Indonesian Journal of Cancer Chemoprevention

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ISSN / EISSN : 2088-0197 / 2355-8989
Total articles ≅ 203
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Dyaningtyas Dewi Pamungkas Putri, Erina Rivanti, Raditya Prima Istiaji, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 67-73;

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.
Aji Winanta, Linta Sabila Hanik, Rifki Febriansah
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 74-82;

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.
Pekik Wiji Prasetyaningrum, Endah Puji Septisetyani, Ahmad Suyoko, Adi Santoso
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 99-105;

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.
Roihatul Muti'Ah, Eka Kartini Rahmawati, Tanaya Jati Dhrama Dewi, Alif Firman Firdausy
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 90-98;

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.
Harliansyah Harliansyah, Nunung Ainur Rahmah, Kuslestari Kuslestari
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 106-113;

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.
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;

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.
Ratna Dwi Ramadani, Rohmad Yudi Utomo, Adam Hermawan, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 46-56;

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.
Jackson Jackson, JohnI Halim, Rezky Anggraeni,
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 57-66;

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.
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;

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.
Eva Annisaa', Widyandani Sasikirana, Nuraini Ekawati, Intan Rahmania Eka Dini
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 21-27;

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.
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