Indonesian Journal of Cancer Chemoprevention

Journal Information
ISSN / EISSN : 2088-0197 / 2355-8989
Current Publisher: Indonesian Journal of Pharmacy (10.14499)
Total articles ≅ 198
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Ratna Dwi Ramadani, Rohmad Yudi Utomo, Adam Hermawan, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 46-56; doi:10.14499/indonesianjcanchemoprev12iss1pp46-56

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.
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; doi:10.14499/indonesianjcanchemoprev12iss1pp11-20

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.
Alireza Heidari
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 1-10; doi:10.14499/indonesianjcanchemoprev12iss1pp1-10

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.
Roihatul Mutiah, Alif Firman Firdausy, Yen Yen Ari Indrawijaya, Hibbatullah Hibbbatullah
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 37-45; doi:10.14499/indonesianjcanchemoprev12iss1pp37-45

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; doi:10.14499/indonesianjcanchemoprev12iss1pp21-27

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.
Jackson Jackson, JohnI Halim, Rezky Anggraeni,
Indonesian Journal of Cancer Chemoprevention, Volume 12, pp 57-66; doi:10.14499/indonesianjcanchemoprev12iss1pp57-66

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; doi:10.14499/indonesianjcanchemoprev12iss1pp28-36

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.
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; doi:10.14499/indonesianjcanchemoprev11iss3pp134-143

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
, Eveline Yuniarti, Tenny Putri, Nurul Qomarilla, Dikdik Kurnia, Mieke Hermiawati Satari, Edhyana Kusumastuti Sahiratmadja, Fathul Huda
Indonesian Journal of Cancer Chemoprevention, Volume 11; doi:10.14499/indonesianjcanchemoprev11iss3pp115-123

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
Roihatul Mutiah, Yen Yen Indrawijaya, Dwi Puspita
Indonesian Journal of Cancer Chemoprevention, Volume 11; doi:10.14499/indonesianjcanchemoprev11iss3pp144-153

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
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