Refine Search

New Search

Results: 217

(searched for: publisher_group_id:1801)
Save to Scifeed
Page of 5
Articles per Page
by
Show export options
  Select all
Roihatul Mutiah, Jauza Ulfah, Muhammad Firman Amrulloh, Arief Suryadinata, Yen Yen Ari Indrawijaya, Ana Rahmawati
Indonesian Journal of Cancer Chemoprevention, Volume 13, pp 1-11; https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp1-11

Abstract:
Helianthus annuus L. (H. annuus) is a potential medicinal plant for cancer therapy. The aims of this study is to identify profile the anticancer activity of H. annuus L. from its leaves, root, stem, and seed as well as to elucidate the apoptosis and cell cycle of the leaves. Ten-gram sample of the powder were extracted by using Ultrasound-Assisted Extraction (UAE) with 200 ml of 96% ethanol by comparison of 1:20 with three times replications. The determination of anticancer activity was used the MTT cell proliferation assay, while apoptosis test and cell cycle were applied with the flowcytometry test. The value of IC50 in 96% ethanol extract in the root and stem was >1,000 μg/mL; seed and leaves were 153.76 μg/mL; and 126.6 μg/mL, respectively. The apoptosis induction of H. annuus leaves extract treatment was 7.17% of apoptosis cells; 90.44% of necrosis, and 2.39% of living cells. The H. annuus leaves extract also significantly caused a decrease of cell percentage in G0-G1 phase (p<0.001) and an increase in G2-M phase (p<0.001). The H. annuus leaves extract had greater potential as anticancer instead of other parts. The adding of H. annuus leaves extract increased the HeLa cell apoptosis, decreased percentage of HeLa cells in G0-G1 phase, and increased percentage of HeLa cells in G2-M phase. Cell cycle mechanism test showed cell cycle arrest in S, G2-M, and M5 phase in 24 h, hence inhibited the mitosis process. Keywords:anticancer, Helianthus annuus L, apoptosis, cell cycle.
Achmad Al Baihaqi, Hasna Siti Munifah Isman, Ganis Fitria Fauziyyah, Rismauli Ruth Natasari Hutabarat, Adi Hartono, Sandra Megantara
Indonesian Journal of Cancer Chemoprevention, Volume 13, pp 33-45; https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp33-45

Abstract:
Prostate cancer is the most common type of cancer diagnosed in men worldwide and the second leading cause of death after lung cancer. Testosterone and dihydrotestosterone (DHT) have been known to play an essential role in prostate cancer. Androgen receptor (AR) binding to the ligand allows homodimerization and translocation to the nucleus, which acts as a transcription factor for androgen-responsive genes such as PSA (Prostate-specific antigen). Although many anti-androgens have been established, including Bicalutamide, Flutamide, and Abiraterone, the problem of non-specific cytotoxicity effects and cancer recurrence due to potential drug resistance remains a significant obstacle to establishing effective therapy. Plantago major L. is one of the plants that can choose anticancer therapy because, based on reports, it has anticancer activity through DNA damage in cancer cells. This study focused on the search for the potential phytochemical activity of Plantago major L. as an anti-androgen, non-cytotoxic, and had significant AR inhibitory activity. This study uses Lipinski prediction (RO5), ADMET prediction, and a structure-based approach with molecular docking techniques using the PDB ID 2AM9 receptor structure and 13 compounds from Plantago major L. as test ligands compared to known AR antagonists. From the research results, Hispidulin has the highest potential as an anti-androgen with binding energy (-9.43 kcal/mol) that is closest to natural ligands and is smaller than Flutamide as a comparison drug. This anti-androgen activity was hypothesized from the similarity of hydrogen bonds with amino acid residues 705-Asn and 711-Gln as key AR residues present in Hispidulin. Keywords:Prostate cancer, Androgen Receptor, Plantago major L., ADMET, In Silico.
Siti Nurkasanah, Aida S.D. Hoemardani, Evlina Suzanna Sinuraya, Puspita Eka Wuyung
Indonesian Journal of Cancer Chemoprevention, Volume 13, pp 12-21; https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp12-21

Abstract:
Skin cancer is a disease that develops in the epidermis of the skin and can be invasive, such as squamous cell carcinoma (SCC). Early detection of squamous cell precancerous can prevent these lesions from progressing to invasive SCC and increase the effectiveness of therapy. 5-fluorouracil (5-FU) is an antimetabolite compound as a pyrimidine DNA/RNA antagonist molecule that induces cell apoptosis. The main objective of this study was to evaluate the effectiveness of the topical 5-FU cream (Dharmais NCH) compared to imiquimod 5% on apoptosis through the expression of caspase-3 in precancerous squamous cells of mouse skin induced by 7,12-dimethylbenzen[a]-anthracene (DMBA)/croton oil treatment. This research assess three differences concentration of 5-FU include 1%, 2%, and 5% on 24 wild type mouse divided into 6 groups including positive control (with carcinogenesis but without treatment), negative control (without treatment; normal), carcinogenesis with treatment 5-FU cream (1%, 2%, and 5%) or 5% imiquimod cream. Two-stages carcinogenesis induced by DMBA and followed by croton oil. The expression of caspase-3 was analyzed using immunohistochemistry. Statistical analysis was performed by one-way ANOVA using SPSS version 23. The induction of two-stages of carcinogenesis (weeks 1 to 10) caused papilloma lesions on the skin of mouse. Furthermore, 5-FU treatment for 4 weeks (weeks 11 to 14) showed a decrease in the cumulative number of papillomas (p0.05). The apoptotic effect of 5-FU treatment on precancerous skin squamous cell lesions in mouse was not significantly different from the standard treatment using imiquimod. This suggests that 5-FU treatment has potential as a future therapy in squamous cell precancerous skin lesions. Keywords: 5-fluorouracil, caspase-3, squamous cell precancerous, skin, topical treatment.
Endah Puspitasari, Nuri Nuri, Indah Yulia Ningsih, Bawon Triatmoko, Dewi Dianasari
Indonesian Journal of Cancer Chemoprevention, Volume 13, pp 55-60; https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp55-60

Abstract:
Tithonia diversifolia has been showed to be cytotoxic and antiproliferative on colon cancer, glioblastoma, hepatoma, kidney cancer, breast cancer, lung cancer, melanoma, leukemia, ovary cancer, prostate cancer, and stomach cancer cell lines, but not on cervical cancer cells yet. Our research aimed to determine the cytotoxicity and antiproliferative activity of T.diversifolia leaf ethanolic extract on HeLa cervical cancer cell line. The cytotoxicity and the antiproferative activity assay were done using MTT method for 24 h for cytotoxic assay; and series of 24, 48, and 72 h for antiproliferative assay. The cytotoxic activity was analyzed using IC50, while the antiproliferative assay was analyzed based on the proliferation kinetics. All assays were done in triplicate. T.diversifolia leaf ethanolic extract exhibited strong cytotoxic activity on HeLa cervical cancer cell lines with the IC50 of 97.839±10.120 μg/mL. The cytotoxic activity was dose dependent. Based on the proliferation assay, the antiproliferative activity was stronger as the incubation time and the dose increases. T.diversifolia leaf ethanolic extract showed strong cytotoxic and antiproliferative activity on HeLa cervical cancer cell lines. Keywords:T.diversifolia leaf ethanolic extract, cytotoxicity assay, antiproliferative assay, HeLa cervical cancer cells.
Hanaan Emilia Adi Hastuti, Midori Rahmadhany Putri Adisusilo, Yusufia Asmarani Ashar, Edy Meiyanto, Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention, Volume 13, pp 22-32; https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp22-32

Abstract:
Matrix metalloproteinase-9 (MMP9) has an essential role in cervical cancer metastasis. Sappan wood extract (SWE) from Caesalpinia sappan contains metabolites that have pharmacological effects and can potentially inhibit metastasis by targeting the protein markers. This research aims to discover the potency of compounds in C. sappan as chemopreventive agents for metastasis in cervical cancer by targeting MMP9. SWE was obtained by maceration with methanol and analyzed using thin layer chromatography (TLC). In vitro cytotoxicity test of SWE on HeLa cells was performed by direct counting method. MMP9 expression profiles and survival rates in cervical cancer patients were explored through bioinformatics studies by the GEPIA database. The CMAUP and PubChem databases were used to obtain the metabolomic profile of SWE. SWE compounds’ activities on target proteins were obtained through KNIME software, while its interaction with MMP9 was analyzed using molecular docking with MOE software. We obtained SWE with a yield of 9.7% w/w. The extract contains brazilin and is indicated by the spot appearance at Rf 0.375. The cytotoxicity of SWE against HeLa cells was considered potential as the IC50 value was 54.93 μg/mL. Based on the bioinformatics analysis, there is a significant difference in MMP9 expression between normal and cervical cancer tissue. The patient’s survival probability decreased if MMP9 was overexpressed. The molecular docking results showed that active compounds of SWE bind to the MMP9 inhibition site with higher affinity compared to the native ligand. This study reveals that SWE potential to be developed as a chemopreventive agent through metastasis inhibition in cervical cancer by targeting MMP9. Keywords:Caesalpinia sappan L., metastasis, bioinformatics, molecular docking, MOE.
Binar Asrining Dhiani, Nunuk Aries Nurulita, Fitriyani Fitriyani
Indonesian Journal of Cancer Chemoprevention, Volume 13, pp 46-54; https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp46-54

Abstract:
Breast cancer is the highest mortality cause in women with cancer. Protein-protein docking for target-based screening is an effective approach in breast cancer drug discovery via estrogen receptor (ER) signaling. TRIM56, an E3 ubiquitin protein ligase, can bind to and stabilize ER alpha. Thus, drug screening that can inhibit or weaken the interaction between ER alpha and TRIM56 is promising to obtain novel yet specific breast cancer drugs. In this study, we performed protein-protein docking studies for ER alpha and TRIM56 interaction and virtual screening for FDA-approved drugs from the ZINC database against ER alpha and TRIM56 complex protein model structure. We utilized Cluspro 2.0, PyRx 0.8, and Pymol 2.4.1 to conduct protein-protein docking, virtual screening, and model structure visualization. PIP and PLIP software were also applied to analyze the amino acid residue between proteins or protein-ligands. Based on the protein-protein docking, ER alpha and TRIM56 established interaction. Utilizing this complex protein as a macromolecule in the virtual screen of 1071 molecules of FDA-approved drugs, we obtain the top five lowest binding energy molecules i.e., dutasteride, dihydroergotamine, nilotinib, ergotamine, and bromocriptine. In addition, the energy binding affinity between ER alpha-dutasteride complex with TRIM56 was weakened in the presence of dutasteride. In conclusion, protein-protein docking between ER alpha-TRIM56 was able to select FDA-approved drugs that could bind to the complex, and dutasteride binding to ER alpha-TRIM56 complex weakened the interaction. Keywords: protein-protein docking, estrogen receptor alpha, TRIM56, breast cancer, ubiquitin.
Amel Elbasyouni, Leila Saadi, Abdelkarim Baha
Indonesian Journal of Cancer Chemoprevention, Volume 13, pp 61-70; https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp61-70

Abstract:
The inhibition of DNA methyltransferase-1 enzyme can strongly decrease the capacity of cells to enhance the tumour-genesis process. Members of the Estrogen-Related Receptors family regulate several elements of cellular metabolism. These are orphan nuclear receptors that regulate a wide range of functional gene networks involved in breast carcinogenesis and the regulation of associated methionine and folate cycles, providing a proven direct relationship to DNA methylation as a result. Moreover, dietary phytochemicals, such as Curcumin, can involve epigenetic modification, which may decrease the development of many types of cancer, especially breast cancer in women. We conducted this study to investigate the effect of Curcuma (PubChem ID: 969516) on the epigenetic modification and inhibition of the DNA methyltransferase-1 (PDB ID: 3PTA) activity and Estrogen-Related Receptors (PDB ID: 1XB7) using Molecular docking approach and computational tools that may inform whether the Curcuma could provide this protective anticancer effect or not. Interestingly, the DNA methyltrasferase1-Curcumin and Estrogen-Related Receptors-Curcumin complexes display a docking score of -6.9 and -7.1 kcal/mol, respectively. Furthermore, Curcumin displays hydrogen, Pi-Cation, Pi-Anion and Van der Waals bonds with active site residues of the targeted molecules. By targeting DNA methylation via the combined inhibition of estrogen-related receptors and DNMT1, our research opens up a new therapeutic path for breast cancer treatment. Keywords:curcumin, breast cancer, epigenetic, molecular docking, treatment.
Sri Handayani, Dina Aprilia, Khoirun Nisa, Vita Taufika Rosyida, Martha Purnami Wulanjati, Anjar Windarsih, Cici Darsih, Andri Frediansyah, Sari Haryanti
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 170-179; https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp170-179

Abstract:
Protective agent for hepatotoxicity is still a great challenge in the management of liver diseases. Aloe vera is a beneficial plant that has been studied for food supplements, cosmetic and herbal medicine. Aloe vera contains many compounds which have a role in body health including polysaccharides, phenolic, flavonoid, terpenoid, amino acid, and several minerals. There have been compelling evidences that natural phytochemicals and their derivatives have hepatoprotective activities. Information of the aloe vera and its mechanism of action for possible hepatoprotective activities, including in silico, in vitro, and in vivo studies were obtained from Pubmed, Science Direct, Scopus, and Google scholar search engines. This current review was focusing on the possible contribution of compounds inside aloe vera gel and the suggestion of its mechanism on protective effect, especially for liver. The complexity of monosaccharides composition, backbone structures, acetyl group, and molecular weight of aloe polysaccharides have possible correlations with its hepatoprotective effect. Most of the hepatoprotective mechanisms of aloe compounds are related to their protective effect against inflammation and oxidative stress. Several compounds may have combination effects or several targets lead to synergistic effects. Keywords:Aloe vera, food supplement, hepatoprotective, liver disease, mechanism of action.
Hamzah Hamzah, Thomas Erwin Christian Junus Huwae, Chodidjah Chodidjah
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 123-129; https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp123-129

Abstract:
Post-menopausal osteoporosis is a degenerative disease among post-menopausal women. In Indonesia, women over 50 years old get post-menopausal osteoporosis.The therapy should be comprehensive and continous. Bisphosphonate therapy is one of the most preferable therapeutic option for maintaining bone density. Calcium and vitamin D have a role in increasing osteoblastic activity. The objective of this study was to describe the vitamin D and calcium in bone mineral density (BMD) of hip and spine in postmenopausal woman with biphosphonat therapy. This study is a cross-sectional, observational analytic. The subject were female patients with post-menopausal osteoporosis treated in clinic of RSUD dr. Saiful Anwar Malang, who had received routine bisphosphonate for at least 1 year. The method was collecting the patient data, who received oral and injectie bisphosphonate therapy, serial BMD test,hip and spine, vitamin D and calcium level in serum test. Total sample 25 participan, the association between BMD change (Δ BMD), vitamin D and calcium level, were analyzed.with Chi Square test then continued using Spearman correlation test. Vitamin D levels in Δ BMD Spine in participants was less <30 ng/ml, mean 16.8+6.95 14 respondents (56%), and 6 respondens (24%) 10.05+5.28, normal vitamin D levels were 5 respondents (20%) mean 34.16+5.10. Vitamin D levels in Δ BMD Hip in participants was less <30 ng/ml, mean 15.19+7.7 12 respondents (48%), and 8 respondens (32%) 12.30+5.57, normal vitamin D levels were 5 respondents (20%) 33.66+5.40. Calcium levels in BMD spine 9.60+0.45, 14 respondents (56%), and 11 respondens (44%) 9.59+0.52. There is a significant and moderate relationship between vitamin D levels with Δ BMD spine (p=0.009, r=0.564) and Hip (p=0.039, r= 0.480) T Blood calcium levels with Δ BMD changes unrelated (normal). There is a significant association between vitamin D levels spine and Hip Δ BMD. Blood calcium levels with Δ BMD changes unrelated. Keywords:Osteoporosis, Bisphosphonate, Vitamin D levels, Calcium levels.
Roihatul Mutiah, Tanaya Jati Dharma Dewi, Arief Suryadinata, Kesimira Qonita
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 148-160; https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp148-160

Abstract:
Citrus maxima or pomelo is a plant that has potential as an anticancer because it contains flavonoids. One of the targets of breast anticancer receptors is the HER-2 protein. This research aims to determine the anticancer activity, the toxicity of the compound, and the prediction of physicochemical properties of flavonoids contained in Citrus maxima through in silico approach. Flavonoid compounds were screened using SwissADME with Lipinski's rule of five, Torsion, TPSA, and P-Gp Non-Substrate. Compounds that passed the screening were carried out molecular docking to the HER-2 receptor (PDB ID: 3PP0) using the Molegro Virtual Docker (MVD). The HER-2 receptor (GDP ID: 3PP0) was declared valid because it had RMSD<2Å. The results showed that there were 11 flavonoid compounds that passed the screening and had a lower rerank score than the comparison compound Trastuzumab. Toxicity was predicted using the Protox II online tool and the results showed that the flavonoid compounds were in the safe limits, namely classes 5 and 3. Based on this research, it can be concluded that acacetin, diosmetin, honyucitrin, isosinensetin, nobiletin, sinensetin, and tangeretin can be candidates for breast cancer drugs based on natural ingredients. Keywords:breast cancer, Citrus maxima, HER-2, in silico.
Ratih Kurnia Wardani, I Made Rhamandana, Christina Mutiara Putri Gono, Muthi Ikawati
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 137-147; https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp137-147

Abstract:
Overexpression of geranylgeranyl diphosphate synthase 1 (GGPS1) is an unfavorable prognosis in liver cancer development. The side effects of therapeutic standards encourage the development of therapeutic agents from herbal materials. Citrus peels are rich of phytochemical compounds, especially citrus flavonoids, that possess cytotoxic activities. This study aimed to determine the potential of citrus flavonoids as chemopreventive agents targeting GGPS1 protein by phytochemical and bioinformatic studies. Dried peels of Citrus reticulata were extracted by hydrodynamic-cavitation method followed by identification of compounds using thin layer chromatography (TLC). The expression level of GGPS1 was obtained from UALCAN, while its correlation with survival rate was obtained from the GEPIA. Prediction models regarding the potential inhibitors of citrus peel compounds against GGPS1 were obtained through KNIME and ChEMBl, followed by literature studies on chemopreventive activity of citrus flavonoids. The molecular docking was used to predict the molecular interaction followed by tracking of target genes that were positively correlated with GGPS1 by SwissTargetPrediction. Yielded 75% (v/v), the extract positively contained citrus flavonoid with hesperidin as comparison. Overexpression of GGPS1 significantly reduced the survival rate of liver cancer patients (p value=0.019). Four citrus flavonoid compounds, namely tangeretin, nobiletin, hesperidin, and naringenin showed potential inhibition to GGPS1. The molecular docking showed that tangeretin had a strong affinity compared to the native ligand and zoledronic acid, as positive control. PARP1, CSNK2A1, TNKS2, and GSK3B were clarified as targeted genes for tangeretin and nobiletin that positively correlated with GPPS1. In vitro and in vivo studies will validate our findings and support the development of citrus peel extract with rich flavonoid contents as a chemopreventive agent. Keywords:geranylgeranyl diphosphate synthase 1 (GGPS1), liver cancer, hydrodynamic-cavitation, citrus flavonoid, bioinformatic.
Sri Susilowati, Neni Susilaningsih, Catharina Suharti
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 130-136; https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp130-136

Abstract:
Apoptosis is one of the anticancer targets. Currently, the concomitant use of phytotherapy products and chemotherapy regimens is common in breast cancer patients. The purpose of this study was to examine the apoptotic effect of adding beetroot extract to the neoadjuvant Adriamycin Cyclophosphamide (AC) regimen by observing the expression levels of p53 and caspase 3 in tumor tissue from mammary adenocarcinoma rats. Twenty-four rats that succeeded in growing tumor nodules were randomly divided into 4 treatment groups: without treatment, AC only treatment, AC plus beetroot extract at dose of 25 and 100 mg/kg BW, respectively. AC was given 4 cycles in doses of 5 and 50 mg/kg body weight intraperitoneally every week. Tumor tissue was dissected at 4th week for examination of p53 and caspase 3 expression levels using the qRT-PCR method. The addition of beetroot extract at doses of 25 and 100 mg/kg BW in the neoadjuvant AC regimen showed significantly higher levels of p53 and caspase 3 expression than those with AC treatment alone. These results proved that beetroot extract has a synergistic effect with neoadjuvant AC regimen by increasing tumor cells apoptosis. Keywords:Beetroot extract, Adriamycin, Cyclophosphamide, apoptosis, p53.
Bayu Anggoro, Dennaya Kumara, Dhella Angelina, Muthi Ikawati
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 114-122; https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp114-122

Abstract:
Citrus flavonoids have been known for their vast biological activities including chemoprevention activities. However, the organic solvent extraction system limits its potential utilization. We recently adopted a hydrodynamic-cavitation method to extract citrus flavonoids from citrus peels. In this study we verified the high flavonoid content of the hydrodynamic-cavitation extract from Citrus reticulata peels and explore the potency of its citrus flavonoid contents as targeted chemoprevention agent for breast cancer by using bioinformatics. Based on a thin layer chromatography, the extract positively yielded high content of citrus flavonoids represented by hesperidin. The toxicity analysis by Protox II Online Tool revealed that hesperidin as the major citrus flavonoid in the extract was considered safe with a predicted LD50 of 12,000 mg/kg. We then further exploring citrus flavonoids’ capacity in targeting MAP1LC3A, a key protein in autophagy. UALCAN analysis validated that low expression of MAP1LC3A is associated with low survival rates in breast cancer patients. Limonin, hesperidin, narirutin, neohesperidine, and naringin are flavonoids from citrus peels that predicted to have inhibitory activity against Protein Kinase A (PKA), a negative upstream of MAP1LC3A, calculated by KNIME. Citrus flavonoids scoparone, cirsimaritin, 4',5,7-trimethoxyflavone, eupatorine, and hesperidin were also exhibit similar structure to an agonist of ATG4B, a protein that plays a role in MAP1LC3A activation. Furthermore, eupatorine, hesperidin, and cirsimaritin displayed a high affinity to ATG4B based on a molecular docking. We concluded that citrus flavonoids from citrus peels are safe to normal cells, and the citrus flavonoids potentially targets MAP1LC3A by inhibiting PKA and acting as ATG4B agonists. Thus, this extract-contained flavonoids from citrus peels is potential to be investigated further as a chemoprevention agent by inducing autophagy, especially for breast cancer. Keywords:Citrus reticulata, citrus flavonoid, autophagy, MAP1LC3A, breast cancer.
Dicky Rizky Febrian, Joko Setyono, Muhamad Salman Fareza, Nur Amalia Choironi, Arif Fadlan, Sarmoko Sarmoko
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 161-169; https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp161-169

Abstract:
Breast cancer is a second deadly cancer after lung cancer worldwide. Progression of cancer is driven by mutated cancer drive gene such as ARHGAP35. This study aims to analyze the role of ARHGAP35 in the growth and development of breast cancer cells. ARHGAP35 expression level was analyzed using Oncomine (p-value<1E-4; gene rank top 10%). Overall survival (OS) and disease-free survival (DFS) were evaluated by using GEPIA (median cutoff; HR displayed with 95% CI). STRING was used for analyzing the protein-protein interaction network, while WEBGESTALT for KEGG pathway and gene ontology (GO) of ARHGAP35 and associated proteins and cBioPortal for gene mutation. ARHGAP35 was overexpressed in several types of breast cancer, namely invasive ductal breast carcinoma (IDC), invasive ductal and lobular breast carcinoma (IDLC), invasive lobular breast carcinoma (ILC), male breast carcinoma, and mixed ductal and lobular carcinoma (MDLC). High expression of ARHGAP35 had significantly lower OS (p=0.045) compared to low expression of ARHGAP35 and the difference in DFS was not significant (p=0.98). ARHGAP35 interacted with RHOA, RHOB, RHOC, RHOD, RASA1, RND1, RAC1, CDC42, FYN and SRC. KEGG pathway and GO analysis showed that these proteins are highly involved in actin-based processes through adherent junction, axon guidance, focal adhesion, regulation of actin cytoskeleton, and tight junction. Mutation rate analysis showed 34 missense, 29 truncating, 3 fusion, and 1 in frame on ARHGAP35. Taken together, ARHGAP35 may involve in the growth and development of breast cancer through regulation of actin cytoskeleton pathway. Keywords:ARHGAP35, breast cancer, KEGG pathway, mutation rate, actin cytoskeleton.
Pekik Wiji Prasetyaningrum, Endah Puji Septisetyani, Ahmad Suyoko, Adi Santoso
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 99-105; https://doi.org/10.14499/indonesianjcanchemoprev12iss2pp99-105

Abstract:
The C2C12 myoblasts are adult murine muscle stem cells which isolated after injury to induce muscle regeneration. The cells are widely used in pharmaceutical and biological researches to represent skeletal muscle cells. In our laboratory, we utilize the cells for glucose uptake assay after insulin treatment and studying the muscle regeneration. In this study we conducted recloning of C2C12 cells by limiting dilution cloning (LDC) and investigated the biological properties incuding cell proliferation, adhesion and differentiation of the clonal cells in comparison to the parental cells. Cell proliferation rate had been determined by WST assay, cell adhesion had been observed after cell detachment by EDTA and cell differentiation into multinucleated myotube had been investigated after induction and incubation with horse serum. As results, two clonal derivatives of C2C12 myoblast cells had been retrieved by LDC and used for cell assays. Moreover, the results indicated that parental cells showed faster proliferation rate and better differentiation ability than that of clonal cells. In the contrary the parental cells exhibited weaker adhesion rate than clonal cells. To conclude, C2C12 parental cells are better for performing the glucose uptake or muscle regeneration assays since they showed better differentiation capability.Keywords: C2C12 cells, cells differentiation, myoblast, myotube, recloning.
Aji Winanta, Linta Sabila Hanik, Rifki Febriansah
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 74-82; https://doi.org/10.14499/indonesianjcanchemoprev12iss2pp74-82

Abstract:
Parijoto (Medinilla speciosa (Reinw ex BL)) is one of the Indonesian indigenous plants widely used as traditional medicine. A previous study showed that ethanol and methanol extracts of Parijoto fruit could inhibit T47D breast cancer cells. This study explores the antioxidant and cytotoxic activities of Parijoto fruit extract and fractions on HeLa cell line. The fruits were extracted using ethanol 70% and fractionated by hexane and ethyl acetate. Furthermore, the fraction was analyzed for secondary phytochemical metabolite content using thin-layer chromatography and staining reagents. The antioxidant and cytotoxic activities were determined using the DPPH scavenging assay and the MTT assay, respectively. The ethanol extract and fraction contained flavonoid and tannin compounds. Ethanol extract, ethanol fraction, and ethyl acetate fraction of Parijoto fruit had an antioxidant activity with IC50 values of 77.3, 88.64, and 46.61 μg/mL, respectively. Ethyl acetate fraction showed the highest activity on HeLa cells with an IC50 value of 45.57 μg/mL compared to ethanol extract, ethanol fraction and n-hexane fraction with an IC50 value of 233.43, 700.75, and 534.30 μg/mL, respectively. Based on these results, the ethyl acetate fraction of Parijoto fruit had the potency to be explored further to elucidate their cytotoxicity mechanism in HeLa cells.Keywords: antioxidant activity, cytotoxicity, Medinilla speciosa, Parijoto fruit fractions.
Harliansyah Harliansyah, Nunung Ainur Rahmah, Kuslestari Kuslestari
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 106-113; https://doi.org/10.14499/indonesianjcanchemoprev12iss2pp106-113

Abstract:
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the second leading cause of cancer mortality worldwide. Many strategies to discover molecular-based therapy are currently being implemented to overcome the resistance in HCC treatment. Cancer research is more targeted at molecular level of natural ingredients treatment as chemoprevention to reduce carcinogenesis risk. One of the natural compounds that serve as chemopreventive agent is mangosteen. α-Mangosteen, a xanthone commonly found in the fruit hull of Garcinia mangostana Linn, possess as an antioxidant. This study aims to determine the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl (PC) as the biomarkers of oxidative stress on untreated HepG2 cells compared to α-mangosteen-treated HepG2 cells. The results indicated that α-mangosteen has a cytotoxic effect on HepG2 cells with IC50=242.58 μg/mL and reduced ROS level 23.15±4.29% at 200 μg/mL. The MDA level of HepG2 cells was not significantly higher than on WRL-68 by 7.6%, 17.93%, 28.8%, 35.32%, and 61.95% at 100, 200, 500, 800, and 1000 μg/mL respectively. α-Mangosteen at 100 and 200 μg/mL reduced protein carbonyl by 76.24 and 79.84% in HepG2 cells line while compared to normal liver cells line (WRL-68) significantly (P<0.05). In conclusion, α-mangosteen reduced levels of ROS, MDA and PC. Therefore, α-mangosteen is a potential anti-cancer agent through oxidative stress inhibition.Keyword: free radical, HepG2 cells, α-mangosteen, oxidative stress.
Roihatul Muti'Ah, Eka Kartini Rahmawati, Tanaya Jati Dhrama Dewi, Alif Firman Firdausy
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 90-98; https://doi.org/10.14499/indonesianjcanchemoprev12iss2pp90-98

Abstract:
Heliannuols are sesquiterpenes lactone compounds considered to have anticancer activity on the brain cancer. Cancer cell growth is related to overexpression of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) as a pro-angiogenic pathway, which becomes the main factor of angiogenesis and progression. This research aims to predict anti-angiogenic, toxicity, and physicochemical properties of heliannuols. Physicochemical properties were predicted referred to Lipinski’s rule of five (Lipinski RO5), while absorption, distribution, metabolism, and excretion were predicted by using pkCSM online tool. The toxicity of compounds was predicted by using Protox II online tool, and interaction of the ligand with receptors was predicted by conducting validation (VEGFR-2 (PDB ID: 3WZE)) and molecular docking using Molegro Virtual Docker (MVD). The result revealed that Lipinski RO5 compatible heliannuols had the lowest LD50 2148 mg/kg predictive LD50 predictive values of heliannuol D. The docking result was described by rerank score (RS), representing the bound energy form and compares with Sorafenib as a reference drug. Five medium strength VEGFR-2 chemical substances with rerank score: heliannuol A -56.9496, heliannuol heliannuol B -70.83646, heliannuol C -61,3292, heliannuol D -49.61646, and heliannuol E -75.5164. No better rerank score was recorded for all inhibitors than sorafenib (-128.0683). The heliannuols interacted with amino acid residues Glu885 and Asp1046 that probably conferred the antiangiogenic activity. Taken together, heliannuol D had the greates activity to the target protein and complied Lipinski RO5.Keywords: anti-angiogenic, toxicity, heliannuol, VEGFR-2, brain cancer, molecular docking.
Dyaningtyas Dewi Pamungkas Putri, Erina Rivanti, Raditya Prima Istiaji, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 67-73; https://doi.org/10.14499/indonesianjcanchemoprev12iss2pp67-73

Abstract:
Leunca (Solanum nigrum L.) is a potential source of natural anticancer agents. Solanum nigrum L. ethanolic extract (SNE) has cytotoxic activity in several cancer cell lines. We aimed to evaluate the ability of SNE to increase MCF-7 cell sensitivity to doxorubicin as a chemotherapeutic agent for breast cancer. Cell viability of SNE and its combination treatment with doxorubicin were conducted by 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay, and apoptosis assay was analyzed by Ethidium bromide-acridine orange method. The SNE showed a cytotoxic effect in the MCF-7 cell line with IC50 50 μg/mL. Combination treated DOX-SNE resulted in a combination index (CI) value of 0.21, indicating strong synergism SNE and doxorubicin. The SNE 25 μg/mL combined with doxorubicin 100 nM optimally induced apoptosis of MCF-7 cells. We concluded that SNE is the potential to be developed as a co-chemotherapeutic agent through apoptosis induction though the molecular mechanism need to explore.Keywords: Solanum nigrum L. herb ethanolic extract, doxorubicin, MCF-7, apoptosis.
Popi Hadi Wisnuwardhani, Ratih Asmana Ningrum, Apon Zaenal Mustopa, Leggina Rezzy Vanggi, Kudianawati Kudianawati Kudianawati
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 28-36; https://doi.org/10.14499/indonesianjcanchemoprev12iss1pp28-36

Abstract:
Colorectal cancer (CRC) is one of the leading causes of cancer and cancer-related deaths worldwide. Lactic acid bacteria (LAB) are bacteria that have potential activity as an inhibitor of the growth of colorectal cancer, and also has been widely used and was very useful for consumption. In our previous study, we isolated various LAB from Indonesian traditional fermented food. This study aims to determine the potential of LAB as an anticancer agent by determining the antioxidant activity and cytotoxicity assay of colon cancer in the WiDr cell line. This study used extracellular extract of various LAB. We use the Diphenylpicrylhydrazyl (DPPH) method to determine the antioxidant activity and 3-(4,5'dimethylihiazol-2-yl),2.5-di-phenyl-relrrzolium bromid (MTT) assay to study cytotoxicity activity. The viability cell staining also applied to detect unviable cells. The results informed that the highest antioxidant activity was shown by S.34 LAB with 81% activity. The S.34 also showed cytotoxicity activity with 73% of WiDr viable cell at a concentration of 200 μg/mL of LAB extract. Based on the results of the study, it can be concluded that the S.34 LAB from Bekasam may inhibit the proliferation of WiDr cell lines and It had the highest antioxidant activity comparing to other LAB samples.Keywords: Lactic Acid Bacteria, colorectal cancer, anticancer, antioxidant, WiDr cells.
Alireza Heidari
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 1-10; https://doi.org/10.14499/indonesianjcanchemoprev12iss1pp1-10

Abstract:
In the current paper, optimization of Tri Propyl Amine (TPrA) concentrations and Os–Pd/HfC nanocomposite as two main and effective materials in the intensity of synchrotron for tracking, monitoring, imaging, measuring, diagnosing and detecting cancer cells are considered so that the highest sensitivity obtains. In this regard, various concentrations of two materials were prepared and photon emission was investigated in the absence of cancer cells.Keywords: Synchrotronic Biosensor, Os–Pd/HfC Nanocomposite, Photomultiplier, Hafnium(IV) Carbide (HfC) Nanoparticles, Tracking, Monitoring, Imaging, Measuring, Diagnosing, Detecting, Cancer Cells, Osmium bis(2,2'–bipyridine)chloride.
Jackson Jackson, JohnI Halim, Rezky Anggraeni,
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 57-66; https://doi.org/10.14499/indonesianjcanchemoprev12iss1pp57-66

Abstract:
Ameloblastoma, a tumor located in the jaw, grows slowly but locally invasive. Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-α. RANKL plays an important role in generating osteoclastogenesis. MMPs degrade the extracellular matrix. TNF-α can induce the formation of osteoclast and modulate the MMPs. In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed.Keywords: Ameloblastoma, RANKL, MMPs, TNF-α.
Ratna Dwi Ramadani, Rohmad Yudi Utomo, Adam Hermawan, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 46-56; https://doi.org/10.14499/indonesianjcanchemoprev12iss1pp46-56

Abstract:
Breast cancer is the most common type of cancer causing mortality for women due to metastasis. More than 50% of breast cancer patients are suffered lung metastases. One strategy to target the cancerous cell is Boron Neutron Captured Therapy (BNCT) which showed high affinity toward cancer cells and reported to have anti-proliferative as well as anti-metastatic activities. Pentagamaboronon-0 (PGB-0) is a curcumin analogue substance which had reported to exert anticancer activities against Her-2 expressing as well as triple negative breast cancer cells. Despite its great potency as BNCT agent candidate, this compound also exerted several anticancer properties. Complex formation of this substance with sorbitol was achieved to improve the solubility and maximize compound’s delivery to the target cells. This study aimed to investigate the ability of Pentagamaboronon-0-Sorbitol (PGB-0-So) to modulate cell cycle and induce apoptosis especially through the mechanisms of reactive oxygen species (ROS) modulation. The 3-(4,5-dimethylthiazzol-2yl)-2,5-diphenyltetrazolium (MTT) cytotoxicity assay of PGB-0-So against 4T1 breast cancer cell line were found to exert potential effect in dose-dependent manner with lethal concentration (IC50) values of 39 μM. The cytotoxicity of PGB-0-So complex was found to be increased considerably compared with that of PGB-0. Cell cycle modulation identified using propidium iodide (PI) staining showed cell accumulation in S phase following treatment with PGB-0-So. Apoptosis induction assay analyzed using flowcytometer with Annexin V and PI staining on its IC50 dose was found to induce programmed cell death (apoptosis). The sub-IC50 treatment of this compound was also improved the cellular ROS level which also took role in apoptosis induction. These findings suggest that PGB-0-So is potential as an anticancer agent. Keywords:Curcumin analogue, PGB-0-So, Anticancer, 4T1 cell line, ROS modulation.
Cecep Suhandi, Ersa Fadhilah, Nurfianti Silvia, Annisa Atusholihah, Randy Rassi Prayoga, Sandra Megantara, Muchtaridi Muchtaridi
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 11-20; https://doi.org/10.14499/indonesianjcanchemoprev12iss1pp11-20

Abstract:
Androgen receptor (AR) is the member of steroid hormone receptor involved in the progression of prostate cancer growth due to receptor over-activation. On the other hand, mangosteen (Garcinia mangostana L.) as a medicinal plant contains xanthone-derived compounds which were known to have cytotoxic activity towards any types of human cancer cells. This research aims to determine xanthone-derived isolates potency from mangosteen as AR antagonists. The study was carried out through molecular docking assay utilizing AutoDock 4.2.6 using androgen receptor obtained from PDB ID 2AM9, testosterone as native ligand, and bicalutamide, flutamide, and nilutamide as reference. The results indicated that three isolates (1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, mangostinone, and trapezifolixanthone) have the highest potency to be AR antagonist seen from the lower bond-free energy value than all of reference ligand. The lowest bond-free energy was provided by mangostinone with a ΔG value of -10.05 kcal/mol. However, the highest difference of residual amino acids interaction with testosterone and similar interaction with bicalutamide was provided by 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, with five different amino acids with testosterone and nine similar amino acids with bicalutamide, respectively. Interestingly, 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone has similar hydrogen bond with the key residue amino acids of AR (705-Asn and 711-Gln) which indicates probably partial agonist activity while mangostinone has the highest amount of hydrogen bond in the absence of hydrogen bond towards key residual amino acids of AR. The results concluded that three specific derived-xanthone compounds were predicted to have activity as AR antagonists.Keywords: Prostate cancer, Androgen receptor, Mangosteen, Xanthone, Molecular docking.
Roihatul Mutiah, Alif Firman Firdausy, Yen Yen Ari Indrawijaya, Hibbatullah Hibbbatullah
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 37-45; https://doi.org/10.14499/indonesianjcanchemoprev12iss1pp37-45

Abstract:
Heliannuols has a benzoxepine ring that produces anticancer activity by the inhibition mechanism of phosphoinositide 3 kinases (PI3K). Heliannuols are a compound that can be found in the leaves of sunflower (Helianthus annuus L.). The purpose of this study is to predict interactions, toxicity, physicochemical, and pharmacokinetics of Heliannuol A, B, C, D, and E based in silico as candidate anticancer drugs. Estrogen receptor beta (ERβ) is a new potential therapy for glioma with an antiproliferative effect. Ligands agonist ERβ have the potential activity to inhibit the proliferation of glioma cells and the discovery of this ligand has opened new therapy through the ERβ to prolong survival in cancer patients. Prediction of physicochemical properties based on Lipinski rules and penetrate in the blood-brain barrier. Receptor validation shows that 2I0G(A) has a smaller RMSD value than 2I0G(B), receptor validation is valid if the RMSD value less than 2. The result of molecular docking shows that Heliannuols comply with Lipinski rules and have low toxicity. Heliannuols also have a similar amino acid with Erteberel, but the rerank score of Erteberel still lower than Heliannuols.Keywords: Helianthus annuus, Heliannuols, estrogen receptor β (ERβ), in silico, toxicity.
Eva Annisaa', Widyandani Sasikirana, Nuraini Ekawati, Intan Rahmania Eka Dini
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 21-27; https://doi.org/10.14499/indonesianjcanchemoprev12iss1pp21-27

Abstract:
Parijoto (Medinilla speciosa Blume) is one of Indonesian plant used for traditional medicine. Previous studies have demonstrated antimicrobial and cytotoxic effects of Parijoto on T47D cells. Therefore, we intended to know the antioxidant and cytotoxic activity of these fractions in 4T1 cell line (a Mus musculus mammary carcinoma). This cancer causes the greatest number of cancer-related deaths This study also investigated the correlation between antioxidant activity and cytotoxicity of Parijoto fractions. Discovering the type of correlation between antioxidant and anticancer activity of botanical extracts could relieve in screening for cytotoxic agent from natural products. The antioxidant and cytotoxic activity investigated using the Diphenylpicrylhydrazyl (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay methods. The result showed that ethyl acetate fraction is the higher antioxidant activity (IC50:1.77 μg/mL) and the higher cytotoxicity (IC50:133.57 μg/mL). There was a strong positive correlation (correlation coefficient=0.957) between antioxidant and cytotoxic activity in 4T1 cell line, but the correlation was not significant (p=0.188).Keywords: Parijoto (Medinilla speciosa Blume), antioxidant, cytotoxic, 4T1 cell line.
Hadi Sunarto, Setyo Trisnadi, Agung Putra, Nur Anna Chalimah Sa'dyah, Arya Tjipta, Chodidjah Chodidjah
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 134-143; https://doi.org/10.14499/indonesianjcanchemoprev11iss3pp134-143

Abstract:
Full-thickness wound are areas damage of skin associated with loss of epidermis and dermis. The wound healing mechanism consists proliferation, migration and remodeling. Hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM) contains lots of soluble molecules, such as protein growth factor and cytokine anti-inflammation. The soluble molecule of HMSCs-CM plays a critical role in wound healing by upregulation of VEGF and collagen synthesis. The objective of this study was to evaluate the effect of HMSCs-CM on VEGF and collagen concentrations in rats with incised wounds. The methods of this study were an experimental animal study with post-test only control group design was performed involving 24 Wistar rats. The rats were randomized into four groups consisting of sham, control and two treatment groups (gel of HMSCs-CM at doses of 200 μL and 400 μL). The VEGF levels and collagen density were analyses using ELISA assay and Masson-trichome specific staining, respectively. One-way ANOVA and Post Hoc LSD were used to analyses the data. The results of this study showed that a VEGF levels was significant increased on day 6 with doses-dependent manner. Interestingly, the VEGF levels gradual decrease on day 9. In addition, the decreased of VEGF levels on day 9 in this study in line with our findings in which we found there was a trend in the decreased of collagen density, it indicated the completion of remodeling phase and there has been an acceleration in wound healing. This study demonstrated that HMSCs-CM were able to regulate VEGF levels and collagen synthesis in accelerate wound healing. The role of HMSCs-CM stimulate cutaneous wound healing should be clarified further.Keywords: hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM), vascular endothelial growth factor, collagen synthesis, paracrine factors
Rohmad Yudi Utomo, Muthi' Ikawati, Dyaningtyas Dewi Pamungkas Putri, Irfani Aura Salsabila, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 11; https://doi.org/10.14499/indonesianjcanchemoprev11iss3pp154-167

Abstract:
The COVID-19 becomes worse with the existence of comorbid diseases such as cardiovascular diseases, metabolic syndromes, inflammation, degenerative diseases, as well as cancer. Therefore, a comprehension approach is needed to combat such comorbid conditions, not only focusing on the virus infection and replication but also directed to prevent the raising comorbid symptoms. This study analyzed the potential natural compounds, especially diosmin and hesperidin, as an anti-SARS-CoV-2 and chemopreventive agent against several COVID-19 comorbid diseases by using an in-silico method. Diosmin and hesperidin together with other natural compounds and existing viral drugs (lopinavir, nafamostat, and comastat) were docked into several proteins involved in SARS-CoV-2 infection and replication namely SARS-CoV-2 protease (PDB:6LU7), spike glycoprotein-RBD (PDB:6LXT), TMPRSS2, and PD-ACE2 (PDB:6VW1) using MOE software. The interaction properties were determined under docking score values. The result exhibited that diosmin and hesperidin performed superior interaction with all the four proteins compared to the other compounds, including the existing drugs. Moreover, under literature study, diosmin and hesperidin also elicit good chemopreventive properties against cardiovascular disorder, lung and kidney degeneration, as well as cancer development. In conclusion, diosmin and hesperidin possess high opportunity to be used for the COVID-19 and its the comorbid diseases as chemopreventive agents.Keywords: chemoprevention, COVID-19, diosmin, hesperidin, SARS-CoV-2 infection
Roihatul Mutiah, Yen Yen Indrawijaya, Dwi Puspita
Indonesian Journal of Cancer Chemoprevention, Volume 11; https://doi.org/10.14499/indonesianjcanchemoprev11iss3pp144-153

Abstract:
Chrysanthemum cinerariifolium (Trev.) is a plant that has potential as an anticancer. This study aimed to predict the inhibitor of estrogen alpha and toxicity of compounds in 96% ethanol extract of C. cinerariifolium leaves in silico. Prediction of the activity of metabolic profiling compounds produced by UPLC QToF MS/MS ethanol extract 96% of C. cinerariifolium leaves towards alpha estrogen receptors (ER-α) (5W9C) was carried out using Molegro Virtual Docker. The docking results showed that the compound (2-Methyl-1,4-piperazinediyl) bis-[(3,4,5-trimethoxyphenyl)-methanone and Azoxystrobin have good activity compared to Tamoxifen, because these compounds have a lower Rerank Score. The activity of the test compound is also shown by the bonding of active amino acids (Arg 394, Asp351, Glu 353, and Val 533). As for the toxicity class based on Globally Harmonized System (GHS) and Lethal Dose 50 (LD50) values, the ten docking compounds had a relatively low toxicity.Keywords: C. cinerariifolium, breast cancer, alpha estrogen, cytotoxic activity, toxicity
Arnold Joseph O. Geronimo, Mari Erika Joi F. Bancual, Karl Anthony L. Ko, Lycon Marie L. Soliba, Jeric John C. Ildefonso, Angelica Mae B. Soriano, Alta Christine Marie M. Tagalog, Nikolai E. Acosta, Vincent S. Ang, Mariebon A. Apigo, et al.
Indonesian Journal of Cancer Chemoprevention, Volume 11; https://doi.org/10.14499/indonesianjcanchemoprev11iss3pp124-133

Abstract:
Cancer is one of the significant causes of mortality worldwide. Studies on antineoplastic drugs focused on natural products have revealed several mechanisms to inhibit cancer cells. Bugnay (Antidesma bunius) leaves showed potentials due to its activity observed against brine shrimp and breast cancer cells. However, there is still limited knowledge about its activity against other human cancer cells. This study focused on determining the phytochemical compounds in A. bunius leaves extract, the free radical scavenging activity of the extract using the Diphenylpicrylhydrazyl (DPPH) method, and in vitro cytotoxic activity against two cancer cell lines, namely HCT-116 human colorectal and A549 human lung adenocarcinoma cancer cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The phytochemicals identified were unsaturated lactones, flavonoids, phenolics, diterpenes, saponins, tannins, carbohydrates, and reducing sugars. The extract showed significant free radical scavenging activity and a direct correlation of activity with concentration levels. It also exhibited cytotoxic activity against HCT-116 human colorectal and A549 human lung adenocarcinoma. Hence, A. bunius leaves have the potential to be a source of antioxidant and antineoplastic compounds. This warrant further isolation of the compounds for chemotherapeutic purposes.Keywords: Antidesma bunius, Bugnay, Cancer, Cytotoxicity, Radical
, Eveline Yuniarti, Tenny Putri, Nurul Qomarilla, Dikdik Kurnia, Mieke Hermiawati Satari, Edhyana Kusumastuti Sahiratmadja, Fathul Huda
Indonesian Journal of Cancer Chemoprevention, Volume 11; https://doi.org/10.14499/indonesianjcanchemoprev11iss3pp115-123

Abstract:
Breast cancer (BC) and cervical cancer (CC) have a high prevalence and mortality rate worldwide. Despite the availability of advanced treatment, resistance to conventional chemotherapies has emerged. Myrmecodia pendens, one of the species of Sarang Semut (local name), possess a potential of antitumor effects by inducing cell death different cancer cell entities. This study aimed to assess anti-tumor activities of n-hexane fraction of M. pendens in inhibiting cell survival and cell migration in BC and CC cells. M. pendens was extracted in methanol then fractionated using n-hexane or ethyl acetate. BC cells including MCF-7 (luminal A), HCC-1954 (HER2+) cells and CC Hela cells were treated with M. pendens extracts to evaluate cytotoxic activity using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay as well as anti-cell migration using scratch assay. We also analyzed inhibitory concentration 50 (IC50) of n-hexane fraction in BC and CC cells. We started with comparing cytotoxicity activities of methanol extract, ethyl acetate and n-hexane fractions of M. pendens. Data showed that the n-hexane fraction was the most potent inducing BC cell death. Therefore, we used the n-hexane fraction for further experiments. Interestingly, IC50 of this fraction in HCC-1954 and Hela cells were lower than in MCF-7 cells, 16; 13 and 60 ppm, respectively. Moreover, the low concentrations of n-hexane fraction inhibited HeLa cells migration, compared to control group (p
Marsya Yonna Nurrachma, Gergorius Gena Maran, Nindya Budiana Putri, Yuni Fajar Esti, Adam Hermawan, Edy Meiyanto, Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention, Volume 11; https://doi.org/10.14499/indonesianjcanchemoprev11iss3pp103-114

Abstract:
Fingerroot (Boesenbergia pandurata) is an Indonesian herb, with anti-proliferation and anti-migratory effects against several cancer cells. This study aims to investigate the anticancer property of Fingerroot Extract (FE) in combination with doxorubicin (Dox) against 4T1, a metastatic breast cancer cell lines. FE was prepared by 96% ethanol maceration and characterized by thin-layer chromatography analysis. FE was subjected to a cytotoxicity test with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay alone or in combination with 10 nM Dox against 4T1 cells. Cytotoxic effect was then confirmed by measure reactive oxygen species (ROS) intracellular level using 2’,7’-dichloroflourescin diacetate (DCFDA)-staining flow cytometry-based assay. The anti-migratory effect was observed using scratch wound healing assay and gelatin zymography to investigate matrix metalloproteinase (MMP)-9 expression. FE showed a cytotoxic effect with an inhibitory concentration 50 (IC50) value of 25.5±3.9 μg/mL and performed an improved effect in combination with 10 nM Dox. A single treatment of FE decreased ROS intracellular level, while in combination with Dox, FE increased the ROS intracellular level. Further, at 42 h observation, FE and its combination with Dox inhibited the migration of 4T1 cells with % closure of 82.6 and 82.5, respectively, correlates with a significant decrease of MMP-9 expression. Overall, FE performs a cytotoxic activity and anti-migration activity on 4T1 breast cancer cells.Keywords: Boesenbergia pandurata, cytotoxic, ROS, anti-migration, 4T1
Puguh Indrasetiawan, Sari Haryanti, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 11; https://doi.org/10.14499/indonesianjcanchemoprev11iss3pp168-186

Abstract:
Breast cancer remains as one of the highest causes of cancer-related deaths in the world, including Indonesia. In spite of following the standard protocol therapy, some patients in developing countries consume medicinal herbs as an alternative, complementary, as well as supportive therapies. Several herbs have been recognized to be used for this purpose. Annona muricata, Curcuma longa, Curcuma zanthorrhiza, Curcuma zedoaria, Phyllanthus urinaria, Gynura procumbens, Garcinia mangostana, Morinda citrifolia, and Nigella sativa are some of the plants used as chemopreventive agents with several formulas. Various types of extracts of Annona muricata show anticancer activities in vitro and in vivo. Curcumin, obtained from Curcuma longa and Curcuma zanthorrhiza, acts as p53 regulator and pro-oxidant in MCF-7 cells and also acts as a fatty acid synthase inhibitor in MDA-MB-231 cells. Xanthorrhizol from Curcuma zanthorrhiza has pro-apoptotic activity via modulation of Bcl-2, p53, and PARP-1 protein levels. Curcuma zedoaria contains curcumenone, curcumenol and curdion, which show pro-apoptotic activity in various cell lines and a cancer-induced mouse model. Corilagin and geraniin from Phyllanthus urinaria have different pro-apoptotic effects, in which, the corilagin-caused apoptotic effect is mediated by extrinsic and mitochondrial pathways, whereas geraniin induces apoptosis via ROS-mediated stimulation, both in MCF-7 cells. Thymoquinone from Nigella sativa has been extensively studied for its anticancer activities in recent years. Plants are cultivated, collected and mixed depending on the use as herbal medicines. Active compounds might be formulated if deemed possible. The development of more potential derivatives is also necessary to produce more optimum anti-cancer agents. In conclusion, Indonesian plants and their active constituents show potential activities to be developed as chemopreventive agents.Keywords: Indonesian medicinal herbs, breast cancer, active constituents, molecular targets
Puspaneka Wijayanti, Sri Pramestri Lastianny, Suryono Suryono
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 54-59; https://doi.org/10.14499/indonesianjcanchemoprev11iss2pp54-59

Abstract:
Carbonated hydroxyapatite is frequently used as bone graft material in dentistry. It is highly biocompatible, has osteoconductive properties, and functions as a drug delivery system. Propolis is a natural product from bees that has antibacterial and anti-inflammatory effects and is capable of accelerating wound healing. Incorporating propolis into carbonated hydroxyapatite was expected to enhance the wound-healing process by stimulating fibroblast growth and regenerating alveolar bone in the treatment of periodontitis. The aim of this study was to evaluate the effect of carbonated hydroxyapatite with incorporated propolis on the viability of NIH 3T3 fibroblast cells. This study used three treatment groups [carbonated hydroxyapatite with various concentrations of incorporated propolis (5%, 7.5%, and 10%)] and one control group (carbonated hydroxyapatite with no propolis). An MTT assay was carried out to assess cell viability, and absorbance readings were performed by using an ELISA reader. The data were analyzed by using one-way ANOVA. The results showed significant differences between all groups, and carbonated hydroxyapatite with 10% incorporated propolis has the highest cell viability level of all groups, while the control group has the lowest cell viability. In conclusion, adding propolis to carbonated hydroxyapatite could increase the growth of NIH 3T3 fibroblast cells. Keywords: Carbonated hydroxyapatite, Propolis, NIH 3T3 fibroblast cells, MTT assay
Roihatul Mutiah, Farenza Okta Kirana, Rahmi Annisa, Ana Rahmawati, Ferry Sandra
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 84-89; https://doi.org/10.14499/indonesianjcanchemoprev11iss2pp84-89

Abstract:
Yellow root (Arcangelisia flava (L.) Merr.) has been scientifically known to have potential as an antimalarial, antibacterial, antioxidant, and anticancer. The purpose of this study was to determine the profile of alkaloid content and cytotoxicity of yellow root extract from several regions in Kalimantan. The alkaloid content was tested using the thin layer chromatography (TLC) method with dragendorf reagent. Cytotoxic in vitro test was conducted against WiDr colorectal cancer cells using the 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide (MTT) assay. Yellow roots were collected from Samarinda city, Banjarmasin city, Barito Timur regency, Malinau district, and Balikpapan City. The MTT inhibitory concentration 50 (IC50) of yellow root extracts were 573.308 μg/mL; 582.857 μg/mL; 296.326 μg/mL; 114.119 μg/mL; and 320.162 μg/mL respectively. Results of the compound identification indicated that alkaloid was found in A. flava from all regions. Alkaloids of A. flava extract should be investigated further in order to find possible active agent that could decrease the viability of WiDr colorectal cancer cells.Keywords: Arcangelisia flava, Borneo, colorectal cancer, Kalimantan, WiDr cells.
Banun Kusumawardani, Qonita Nafilah Febi, Malihatul Rosidah, Deri Abdul Azis, Endah Puspitasari, Ari Satia Nugraha
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 97-102; https://doi.org/10.14499/indonesianjcanchemoprev11iss2pp97-10

Abstract:
Flavonoid has potential bioactivity as anticancer agents. The flavonoid of cultivated tobacco (Nicotiana tabacum), locally known as “Kasturi”, leaves was screened for its cytotoxicity against MCF-7 human breast cancer cells and non-transformed Vero cells (African normal cell kidney line) in different concentrations. This study aimed to examine the cytotoxic potential of the flavonoid of Kasturi tobacco leaves against MCF-7 human breast cancer cells. Flavonoid obtained from methanolic extracts of Kasturi tobacco leaves, which have been purified from nicotine. The flavonoid of Kasturi tobacco leaves with concentrations of 20 to 640 μg/mL were exposed to MCF-7 and Vero cells for 24 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Flavonoid of Kasturi tobacco leaves with concentrations of 160 μg/mL decreased the MCF-7 cell viability more than 50%, with an inhibitory concentration 50 (IC50) value of 148.41 μg/mL. Meanwhile, it inhibited 50% of Vero cell viability at 255.35 μg/mL. The flavonoid of Kasturi tobacco leaves has cytotoxic activity on MCF-7 cells, and might be a potential alternative agent for human breast cancer therapy.Keywords: flavonoid, tobacco leaves, human breast cancer cells, anticancer activity
Nunung Ainur Rahmah, Harliansyah Harliansyah, Fransiscus D. Suyatna, Mpu Kanoko, Primariadewi Rustamadji, Joedo Prihartono, Samuel Johny Haryono, Bethy Suryawati Hernowo
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 67-74; https://doi.org/10.14499/indonesianjcanchemoprev11iss2pp67-74

Abstract:
Curcumin has been reported with an in vitro the cytotoxic effect on several human cancer cells. However, reports on the mode of action and detail mechanism of curcumin in breast cancer disease are limited. Hence, curcumin’s effect on the human breast cancer cell line MCF-7 and MDA-MB-468 was investigated. The MCF-7 and MDA-MB-468 breast cancer cells line were given curcumin in several doses. The anti-proliferation activity of curcumin was determined using the MTS cell viability test and caspase-3 activity was used to detect apoptosis using flowcytometry. The expression of Ras-association domain family 1 isoform A (RASSF1A) and Bax protein in cells was evaluated by ELISA analysis. Kruskal-Wallis followed by the Mann-Whitney test and the Spearman correlation tests were used to asses correlation among RASSF1A, Bax, and caspase-3. Cytotoxicity of curcumin on MCF-7 was lower than that of MDA-MB-468 (75.73 μg/mL and 380.79 μg/mL). The concentration of curcumin at 80 μg/mL induced apoptosis mainly through the intrinsic pathway by caspase-3 activation. Curcumin also showed an anti-proliferative activity as shown by the increase of RASSF1A and Bax protein. Curcumin mediates anti-proliferative and apoptotic effect through the activation of RASSF1A and Bax. Our research data adds information about the role of curcumin in epigenetic events through RASSF1A protein.Keywords: Bax, caspase-3, curcumin, MCF-7, MDA-MB-468, RASSF1A
Poppy Anjelisa Zaitun Hasibuan, Rosa Gloria Sitanggang, Robbani Syahfitri Angkat
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 75-83; https://doi.org/10.14499/indonesianjcanchemoprev11iss2pp75-83

Abstract:
Menopause is a hypoestrogenic condition due to decreased function of the ovary. During menopause there is no reserved ovum in the ovary, as a result the synthesis of estrogen by the follicles does not take place. Deficiency of estrogen can lead to discomfort and decrease in the women quality of life. Therefore, supplements from natural resources to reduce menopausal symptoms will be needed. The objectives of the study were to determine the effect of mahogany seeds ethanolic extract (MSEE) on the development of uterus, bone density, and mammae gland proliferation on ovariectomized rats. Extract was made by maceration using 96% ethanol as the solvent, then the study of estrogenic effect was carried out on 30 female rats which were divided into 6 groups. Group 1 (normal control), group 2 (positive control) given estradiol dose of 0.18 mg/kg body weight (BW), group 3 (negative control) given Na-CMC 1% and group 4, 5, 6 given MSEE orally for 14 consecutive days with doses of 50, 100, 200 mg/kg BW. Data were analysed using ANOVA then continued with Tukey HSD Post Hoc test to see the differences between the treatments. The results of the study showed that MSEE was able to increase the weight of the uterus, the length of estrus phase in the estrus cycle, bone density and the mammae gland proliferation of rats. The results concluded that MSEE has phytoestrogenic effect on ovariectomized rats.Keywords: phytoestrogen, ovariectomy, uterus weight, bone density, mammae proliferation
, , Isna Nisrina Hardani, Gita Widya Pradini, Tenny Putri, Eko Fuji Ariyanto
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 90-96; https://doi.org/10.14499/indonesianjcanchemoprev11iss2pp90-96

Abstract:
Cervical cancer is one of the most leading causes of women death. Currently, paclitaxel is still one of the main therapeutic regimens for cervical cancer patients. However, some patients developed to be paclitaxel-resistant. Hence, studies to find out the novel strategies to resolve this problem are important. Generating resistant cancer cell lines can be utilized as the potent tool to evaluate the efficacy of any therapeutic agent toward cancer drug-resistant problems. Current studies describing the methods to establish chemoresistance are lacking. Moreover, study in Indonesia conducting chemoresistance in cell line is limited. This study was aimed to elaborate the characteristics of HeLa cells during generation of paclitaxel-resistant cervical cancer cells. The parental HeLa cells were exposed to an escalating concentration of paclitaxel for a long time period. Subsequently, cells were divided into two groups for the evaluation of resistance characteristics. The values of inhibitory concentration 50 (IC50) and inhibitory concentration 90 (IC90) were analyzed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Our data showed that the longer exposing periods of paclitaxel, the higher IC50 and IC90 values of HeLa cells are. IC90 of paclitaxel in HeLa Pac RB was increased from 69 pM, 440 pM, 2,561 pM and 10,337 pM on 0th, 1st, 2nd, 3rd and 4th months, respectively. Interestingly, the resistant cells were recovered to be paclitaxel-sensitive when they were not being continuously exposed to paclitaxel. In addition, the paclitaxel resistant cells become less sensitive against 5-FU but not doxorubicin, cisplatin and etoposide. We were able to generate cervical cancer HeLa paclitaxel-resistant cell line. These cell line could potentially be utilized for further studies in order to understand the molecular mechanisms of drug resistance in cervical cancer and as a tool for cancer drug discovery.Keywords: cervical cancer, drug resistant cell line, paclitaxel resistant cells, stepwise escalating concentration.
Yoni Astuti, Aulia Primasari
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 60-66; https://doi.org/10.14499/indonesianjcanchemoprev11iss2pp60-66

Abstract:
Colorectal cancer is third rank on the cancer cases in Indonesia. To cure the cancer needs big cost and lot of effort. On the other side, the side effect of medicine or chemotherapy on patient need to reduce. Cancer cell spread to other tissue based on its migration and invasion ability. Citrus reticulata peel contains flavonoid such as Tangeretin and Nobiletin, both of this compounds have anticancer activity. The aims of this study is to reveals the potency of ethanol extract of Citrus reticulata peel on the inhibition of migration on WiDr colon cancer cells. The toxicity of ethanol extract of Citurs reticulata peel on WiDr colon cancer line was measured using 3-(4,5-dimethyltiazol-2-il)-2,5-diphenyltrazolium bromide (MTT) assay and investigate the cell migration was using scratch wound healing assay. The ethanol extract of Citrus reticulata peel showed the value of inhibitory concentration 50 (IC50) was 184.5 μg/mL, this result categorize as moderate cytotoxic. Meanwhile the migration assay showed that the deceleration of migration occurred on 0.5 IC50, 0.33 IC50 and 0.25 IC50 during 24 h and 36 h incubation, event thought there were not significant different (p>0.05). The ethanol extract of Citrus reticulata peel has a potential migration inhibition on WiDr cell line.Keywords: Citrus reticulata, WiDr cell line, migration
, Fania Putri Luhurningtyas
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 22-29; https://doi.org/10.14499/indonesianjcanchemoprev11iss1pp22-29

Abstract:
Antioxidants are agents that can reduce free radicals. Parijoto fruit (Medinilla speciosa) contains flavonoids that could act as an antioxidant. However, those flavonoids are water-soluble and show low bioavailability. Nanotechnology is a potential approach to improve the bioavailability of flavonoids from Parijoto fruit. This study was conducted to determine the antioxidant activity of parijoto nanoparticles with variations of the chitosan, alginate, and chitosan/alginate encapsulants. Secondary metabolites of parijoto fruit were using the maceration method. The synthesis of parijoto nanoparticles was conducted using the ionic gelation method with chitosan, alginate, and chitosan/alginate encapsulation. Parijoto nanoparticle size and distribution were characterized using Particle Size Analyzer (PSA). The formation of nanoparticles in colloids was determined as a percent. The antioxidant activity of nanoparticle was evaluated using Ferric Reducing Antioxidant Power (FRAP) method using a UV-Vis spectrophotometer. Chitosan encapsulation produced nanoparticles with a size of 269.3 nm, pdI 0.372 and transmittance 99.379%. Alginate encapsulation produced a particle size of 366.4 nm, pdI 0.589 and transmittance 99.690%. The combination of chitosan/alginate encapsulants produced a particle size of 187.00 nm, pdI 0.239 and transmittance 99.894%. Parijoto nanoparticles obtained from chitosan, alginate, and chitosan/alginate encapsulant showed strong antioxidant powers indicated by IC50 values 2.442±0.047 ppm, 3.175±0.169 ppm and 2.115±0.045 ppm, respectively. Altogether, our study shows that parijoto nanoparticles are potent as antioxidant agents.Keywords: Alginate, antioxidant, chitosan, FRAP, Medinilla speciosa, nanoparticle
Ivan Arie Wahyudi, Fahri Reza Ramadhan, Rama Insan Kusuma Wijaya, Retno Ardhani, Trianna Wahyu Utami
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 30-35; https://doi.org/10.14499/indonesianjcanchemoprev11iss1pp30-35

Abstract:
The utilization of natural resources, one of which is plants, has been researched as an alternative to synthetic drugs because of their natural content. Potato (Solanum tuberosum L.) peels, the parts of potatoes that are often cut off and discarded, have been reported to have some phenolic compounds and flavonoids in their composition. The extract of potato peels was investigated for its analgesic, anti-inflammatory, and anti-biofilm-forming properties. A hot plate test was conducted to assess the analgesic activity in treatment doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg with paracetamol as the reference drug and distilled water as the negative control, while carrageenan-induced paw edema was used to assess anti-inflammatory activity in treatment doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg with diclofenac as the reference drug and distilled water as the negative control. Anti-biofilm-forming activity was tested by using the crystal violet assay. The results showed that, compared with the negative control, treatment doses of 100 mg/kg and 200 mg/kg significantly (p < 0.05) reduced pain stimuli, whereas a treatment dose of 100 mg/kg, 200 mg/kg, and 400 mg/kg significantly (p < 0.05) reduced the edema volume increment. However, compared with the positive control, paracetamol and diclofenac were associated with the least pain stimulus and the least edema volume increment, respectively. Potato peel extract against S. mutans biofilm formation demonstrated effectiveness (p < 0.05). Based on these data, it can be concluded that potato peel extract has analgesic, anti-inflammatory, and anti-biofilm-forming activities, as demonstrated in this study.
Anif Nur Artanti, Umi Hanik Pujiastuti, Fea Prihapsara, Rita Rakhmawati
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 16-21; https://doi.org/10.14499/indonesianjcanchemoprev11iss1pp16-21

Abstract:
As one of the leading causes of death in worldwide, cervical cancer requires the effective therapies to reduce its mortality rate. One of the chemotherapy agents that frequently used in the treatment is cisplatin. However, due to drug resistance and its side effects, an agent that can be combined with cisplatin is needed. Parijoto fruit (Medinilla speciosa Reinw.ex.Bl) contains secondary metabolites compounds that have potential as anticancer. The study aims to determine the cytotoxic effect of methanol extract of Parijoto fruit calculated from the IC50 value and the synergicity of the combinational treatment with cisplatin evaluated from the Combination Index (CI) value and its cell viability by using MTT assay. Results showed that methanol extract of Parijoto fruit (MEP) performed cytotoxic effect on HeLa cell line with IC50 of 209.6 μg/mL while the value of IC50 of cisplatin against HeLa cells amounted to 12.8 μg/mL. The combination of 26.205 ppm (1/8 IC50) of MEP and 1.601 ppm (1/8 IC50) of Cisplatin performed synergistic effect on HeLa cell line with the CI value of 0.69. From the above results, it can be concluded that MEP is potential as co-chemotherapy agent based on the synergistic cytotoxicity effect with cisplatin.Keyword: cytotoxic, Medinilla speciosa, cisplatin, co-chemotherapy, MTT
Ismanurrahman Hadi, Riris Istighfari Jenie,
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 7-15; https://doi.org/10.14499/indonesianjcanchemoprev11iss1pp7-15

Abstract:
TNBC, one of the sub type of breast cancers was widely known with high tumorigenic and poor prognosis than others. The development of combination agent (co-chemotherapy) with doxorubicin for chemotherapy of TNBC were carried out to decrease doxorubicin side effect and resistance in cancer. This present study aims to explore the co-chemotherapeutic properties of PGV-0 and investigate induction of doxorubicin on apoptosis, senescence and ROS against TNBC. 4T1 Cell line were used as a TNBC in vitro model. Cytotoxic measurement was performed using MTT assay resulting in IC50 values of 52 μM. Meanwhile, the combination of doxorubicin and PGV-0 showed synergistic effect which decreased cell viability of 4T1 better than single treatment of doxorubicin. Apoptosis analysis was performed using annexin V/PI assay indicated that the combination treatment of PGV-0 and doxorubicin increased apoptosis evidence. Senescence detection was carried out using senescence-associated-β galactosidase (SA-β-gal) assay. The results showed that a single treatment of PGV-0 induced cellular senescence and increased senescence cells in combination treatment. Moreover, DCFDA staining showed that PGV-0 increased ROS level at single treatment, whereas combination treatment increased ROS intracellular compared to the positive control of doxorubicin. Based on these results, PGV-0 has potential as a co-chemotherapeutic candidate on TNBC. Keyword: 4T1, PGV-0, Co-chemotherapy, Cytotoxic, Senescence, Apoptosis, ROS
Nur Dina Amalina, ,
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 1-6; https://doi.org/10.14499/indonesianjcanchemoprev11iss1pp1-6

Abstract:
Hyptis pectinata (L.) poit, popularly known in the world as “comb bushmint” is a medicinal plant commonly used for the treatment of throat and skin inflammations, bacterial infection, pain and cancer. The objective of this research is to determine the cytotoxic and antiproliferative effect under Hyptis pectinata ethanolic extract (HPE) treatment on breast cancer cells. The effect HPE of on cytotoxicity was examined by MTT assay on MCF-7 breast cancer cells. This assay also used to determine cell proliferation over 3 days of treatment with 1.5 – 100 µg/mL HPE. HPE showed that exhibited cytotoxic effects with IC50 value of 30 µg/mL for 24 hours and changes the physiological morphology on MCF-7 cells. Interestingly, the treatment of HPE for 48 and 72 hours highly decreases cell viability on MCF-7 with dose and time-dependent manner compared to untreated cells. These results indicate that HPE has antiproliferative activities and maybe the potential to be developed as a natural chemotherapeutic agent.Keywords: Hyptis pectinata (L.) poit extract, cytotoxicity, antiproliferative, MCF-7 cells
, Relita Pebrina, Diah Nurpratami
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 36-45; https://doi.org/10.14499/indonesianjcanchemoprev11iss1pp36-45

Abstract:
Fetal bovine serum (FBS) is a gold standard as a supplement to cell and tissue culture media. This is due to a large number of Growth Factor (GF) contained in FBS. However, the use of FBS is at risk of transferring endotoxins, prions, bacteria and viruses from animals to humans, so it is risky to be used on cell therapy. Human Platelet Lysate (HPL) is a medium that can be developed as an alternative cell growth medium. The advantage of HPL is that it does not contain aggregate platelets so it does not cause the cells to clot. This condition causes HPL to be used as a substitute medium replacing FBS for cell propagation. The use of HPL for cell propagation has been widely reported. However, the use of HPL in cancer cells has not been found. Thus, this study aims to see the effectiveness of HPL as a T47D cell culture medium. The study began with donor selection with criteria for the male sex, the blood type O, the age ≤35 years. Furthermore, the Platelet Concentrate (PC) was processed into HPL then measured pH, total protein and albumin levels. The cell viability was measured using the MTT assay to determine the ability of cell proliferation when propagation using HPL. The doubling time test was carried out as in the cell proliferation test. However, the incubation was carried out for 24 h, 48 h and 72 h and the HPL concentration used was 5%. The result shows that HPL 10% and 20% ability to increase proliferation better than the FBS 10%. HPL with a 5% concentration ability to shortens the doubling time than FBS 10% (doubling time is less than 19.94 h). It this study, cell proliferation is influenced by the pH of HPL and total protein but not by the amount albumin.Keywords: Human Platelet Lysate, Proliferation, T47D cell line, total protein, albumin.
, Sudibyo Martono
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 46-53; https://doi.org/10.14499/indonesianjcanchemoprev11iss1pp46-53

Abstract:
One of the main modalities of cancer treatment is chemotherapy, which uses chemicals that are generally electrophilic. These xenobiotic compounds sometimes does not produce effective response due to activity of glutathione S-transferase (GST) which inactivate the xenobiotics. Several natural phenolic compounds were reported to inhibit GST activity in vitro. Noni fruit (Morinda citrifolia L.) which contains flavonoids and other phenolic compounds such as scopoletin and morindon is proposed to interfere GST activity. This study aimed to analyze the effect of ethanolic extract of Noni fruit in vivo on GST activity in lung rat using 1,2-dichloro-4-nitrobenzene (DCNB). This substrate is a specific for class mu GST. First, rats were administered with ethanolic extract of Noni and dimethylbenz(α)anthracene (DMBA) for two weeks. The cytosolic fraction of lung was isolated then the GST activity was determined by simple kinetic program which was automatically calculated using spectrophotometer. The results showed that ethanolic extract of Noni in 1 and 5% (w/v) of concentration induced class mu GST activity, whereas 10% (w/v) of concentration inhibited class mu GST activity. After a treatment with DMBA, all tested concentrations of ethanolic extract of Noni inhibited class mu GST activity of lung rat significantly. These results indicated that Noni fruit extract can be further developed as a supportive agent of a chemotherapy drug.Keywords: DMBA, GST, Morinda citrifolia L., spectrophotometer.
Haruma Anggraini Muflikhasari, Riris Istighfari Jenie, Ratna Asmah Susidarti,
Indonesian Journal of Cancer Chemoprevention, Volume 10, pp 149-158; https://doi.org/10.14499/indonesianjcanchemoprev10iss3pp149-158

Abstract:
Pentagamavunone-0 (PGV-0), one of the curcumin analogue, is reported to have a cytotoxic effect on various cancer cells. This study aimed to explore the growth inhibitory effects of PGV-0 against highly-metastatic breast cancer, 4T1 cells under stress condition covering 2D and 3D speroid cytotoxic, anti-migration, and suppression of MMP-9. PGV-0 showed cytotoxic effects on 2D and 3D 4T1 cells with IC50value of 49 μM and 26 μM, respectively. In addition, PGV-0 performed anti-migratory effect. The single treatment at 25 μM PGV-0 and 50 μM showed inhibitory effect on cell migration by 54% and 51% respectively. whilst, the combination of PGV-0 at the concentration of 25 μM and 50 μM with doxorubicin significantly inhibited cell migration by 41% and 38%, respectively. The gelatin zymography assay showed that PGV-0 decreased MMP-9 expression both in a single treatment and in combination with doxorubicin. In conclusion, PGV-0 is potential to be developed as anti-tumorigenesis agent on highly-metastatic breast cancers.Keywords: Pentagamavunone-0 (PGV-0), anti-migration, MMP-9, 4T1 cells, spheroid
Indonesian Journal of Cancer Chemoprevention, Volume 10, pp 122-130; https://doi.org/10.14499/indonesianjcanchemoprev10iss3pp122-130

Abstract:
Proto-oncogene tyrosine-protein kinase Src is also known as simply Src is a tyrosine kinase protein which is one of the targets in various cancer therapies such as leukemia. Meanwhile, akar kuning (Arcangelisia flava) has gained significant attention as a medicinal plant that has a cytotoxic effect on various types of cancer cells. This study aims to determine the potential of secondary metabolites of akar kuning as Src inhibitors. Molecular docking was carried out using Autodock Vina 1.1.2 with 2HCK receptors, that quercetin and dasatinib were used as reference ligands. The docking results showed that the highest affinity was shown by berberine with a ΔG value of -9.0 kcal/mol, exceeded quercetin and dasatinib. However, the highest amino acid similarity to quercetin and dasatinib was produced by jatrorrhizine, with 93.33% and 73.91%, respectively. Interestingly, berberine is the ligand with the third-highest similarity after jatrorrhizine and palmatine, while jatrorrhizine has the second-highest affinity after berberine. The results concluded that the combination of berberine and jatrorrhizine is predicted to be optimally used as an Src inhibitor in cancer therapy.
Roihatul Mutiah, Trian Sidha Minggarwati, Risma Aprinda Kristanti, Erna Susanti
Indonesian Journal of Cancer Chemoprevention, Volume 10, pp 131-139; https://doi.org/10.14499/indonesianjcanchemoprev10iss3pp131-139

Abstract:
Eleutherine palmifolia (L.) Merr. is a typical plant found in Central Kalimantan that has been used empirically by the Dayak people as medicine for various diseases, including cancer. The plant contains flavonoid compounds that potentially used as an anticancer. The purpose of this study is to find the most active fraction, indicated by its cytotoxic potency on HeLa cervical cancer cell line, and to identify compounds in E. palmifolia bulbs fraction. E. palmifolia bulbs was extracted by maceration. The extraction with ultrasonic bath and partition fractionation was conducted by using n-hexane, chloroform, and ethyl acetate. Each fraction was tested for toxicity level on HeLa cells using MTT assay. The identification of active compounds was carried out by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). The result showed that based on the IC50 value, the ethyl acetate fraction had the highest bioactivity. IC50 values of n-hexane, chloroform, and ethyl acetate fractions were 250.77±19.01; 720.46±42.38; and 44.34±9.45μg/mL, respectively. The identification of the active compound in ethyl acetate fraction resulted 28 chemical compounds. Compounds with the highest percentage area were isoliquiritigenin and oxyresveratrol. The ethyl acetate fraction of E. palmifolia bulbs is potential to be developed as an anticancer candidate (phytopharmaceutical).Keywords: Compound identification, Anticancer activity, Eleutherine palmifolia (L.) Merr., cervical cancer
Page of 5
Articles per Page
by
Show export options
  Select all
Back to Top Top