Indonesian Journal of Cancer Chemoprevention
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Bioinformatic Test and Pharmacokinetic Profile Prediction of Gnetin-C Compound in Melinjo (Gnetum gnemon L.) Seeds Toward Colorectal Cancer
Full text linkCancer is one of the unresolved health problems in the world, including Indonesia. One of the most common types of cancer is colorectal cancer. Melinjo (Gnetum gnemon L.) is one of Indonesian local commodities which has many benefits including its potential to be developed as an anticancer agent. Through bioinformatics and molecular docking technology, the aim of this study was to investigate the functions of gnetin-C from melinjo against colorectal cancer. PkCSM database were used to search the ADMET (absorption, distribution, metabolism, elimination and toxicity) properties and stitch-string database were used to identify common genes related to colon cancer. During identification of colon cancer related genes, STAT3 protein showed the highest degree score. Furthermore, molecular docking was carried out to find out the interaction between the STAT3 protein and gnetin c compound found in melinjo seeds. From the docking stage, the pose with the best affinity energy was obtained with a docking score of 1,966 kcal/mol. this shows that the compound gnetin c has the potential to be used as a new anticancer agent from natural ingredients.Keywords: Melinjo, Gnetum gnemon, colon cancer, bioinformatics, molecular docking
Co-Chemotherapy Effect of Glycosylated Nanoalbumin Genitri Seed Extract Targeting Induced Apoptotic on Overexpressed HER2+ Breast Cancer
Full text linkHER2-targeted therapy aims to stop proliferation and induced apoptosis. Genitri seeds show anticancer effects and have potential as co-chemotherapy. To maximize bioactive delivery, a glycosylated-nanoalbumin delivery system is used. This research aims to explore the ability of Glycosylated-Nanoalbumin Genitri Seeds (GN-GSE) to induce apoptosis in MCF-7/HER2 cancer cells. The cytotoxic test using the MTT assay showed GSE selectivity (SI=2.7) against cancer cells (IC50 104 μg/mL) and non-toxicity against normal cells (IC50 284 μg/mL). Induction of apoptosis occurs through inhibition of the CDK1 protein which is predicted by molecular docking. GSE has the potential as a synergistic co-chemotherapy with tamoxifen (CI<1) and has good affinity for the CDK1 inhibitory domain. Elaeocarpenine is known to have good affinity with a greater ΔG value (-11.40 kcal/mol) than the native ligand. The GN-GSE formula meets the criteria for nanoparticles with good stability. This research shows that GSE has anti-cancer activity, making it potential as a therapy for HER2 overexpressed breast cancer as well as in a glycosylated nanoalbumin drug delivery system.Keywords: Apoptotic induced, co-chemotherapy, genitri seeds, glycosylated, nanoalbumin
Network Pharmacology and In Vitro Validation of Brazilin as a Potential Apoptosis-Inducing Agent in HBV-Related Hepatocellular Carcinoma
Full text linkHepatitis B virus (HBV) reactivation-related hepatocellular carcinoma (HCC) presents a significant threat due to its potential to cause liver failure and mortality. Consequently, the discovery of novel treatments that offer anticancer efficacy and liver protection is urgently needed. Brazilin, a natural compound, has previously been reported to possess cytotoxic and liver-protective properties. This research aimed to investigate the potency of brazilin in suppressing the growth of HCC cells through in silico and in vitro approaches. Hep3B cells, which harbor integrated HBV DNA, were selected as the HCC model, with PGV- 1 utilized as a positive control. The in silico study used network pharmacology to predict brazilin’s potential gene targets. Cytotoxicity was evaluated using the CCK-8 assay, and apoptosis detection was carried out using Annexin V/PI staining followed by flow cytometry. The analysis predicted that brazilin targets key genes such as SRC, EGFR, AKT1, GRB2, IGF1, ESR1, STAT1, MMP9, JAK2, and PPARG involved in cancer proliferation and metastasis. Proteins such as SRC, GRB2, and MMP9 are overexpressed in TP53-mutated HCC and linked to low survival. Brazilin showed moderate cytotoxicity with an IC50 value of 17 μM at 72 h and significantly induced apoptosis in Hep3B cells. These findings suggest that brazilin is a promising apoptosis-inducing agent for HBV-related HCC.Keywords: brazilin, Hep3B cell lines, network pharmacology, cytotoxic, apoptosis
Prediction of Secondary Metabolite Compounds in Lotus (Nelumbo nucifera Gaertn.) Targeting Androgen-α Receptors for Breast Cancer Treatment Using Molecular Docking
Full text linkBreast cancer (BC) is a malignant tumor that grows in the breast tissue and can spread to other organs. BC is often found at an advanced stage and therefore has a poor prognosis. With 68,858 cases, BC is the most common type of cancer in Indonesia. The development of breast carcinoma is strongly influenced by steroid hormones and their receptors, such as estrogen, progesterone, and androgen. Androgen receptors (AR) are found more (70-90%) compared to estrogen receptors (60-80%) and progesterone receptors (50-70%). Therefore, research on natural compounds that inhibit cancer cell proliferation influenced by AR needs to be increased. The lotus plant (Nelumbo nucifera Gaertn.) has been used as a traditional herbal medicine and food in Asia. Bioactive compounds in lotus have therapeutic potential against BC. In the pharmacophore screening results, five hit compounds were found: isorhamnetin, luteolin, catechin, kaempferol, and apigenin. The compound with the best pharmacophore fit score value is isorhamnetin with a value of 41.31, while the compound with the best binding affinity to AR is kaempferol with a binding affinity of -9.44 and an inhibitor constant of 121.12 nM.Keywords: breast-cancer, androgen-α receptor, lotus, molecular docking
Chemopreventive Properties Curcuma heyneana Rhizome Ethanolic Extract on Hepatocellular Carcinoma Cells, JHH-4
Full text linkHepatocellular carcinoma is the most common type of liver cancer. Curcuminoids are natural polyphenol compounds abundant in Curcuma heyneana ethanolic extract (CHE) and are known to inhibit breast and cervical cancer cell proliferation. Based on previous research, curcuminoid compounds have been studied to inhibit the growth of the liver cancer cell model, HepG2. This study aims to examine the potential of CHE as a chemopreventive agent in liver cancer using JHH-4 cell as a model. CHE was obtained by maceration method using ethanol which was then identified for its phytochemical profile using thin layer chromatography (TLC). Then TLC results were quantified to calculate the levels of compounds present in the CHE based on spot intensity with ImageJ software. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) antioxidant assay was conducted to determine the radical scavenging activity of CHE. Cytotoxic activity of CHE on JHH-4 liver cancer cells was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Extraction produces a yield of 10.2 %w/w. CHE contains 4.52 %w/w curcuminoid compound consisting of 0.49 %w/w curcumin, 3.21 %w/w demethoxycurcumin, and 0.82% w/w bisdemethoxycurcumin. CHE exhibited antioxidant activity with an IC50 value of 378.96 μg/mL, meanwhile ascorbic acid as a positive control has an IC50 value of 8.49 μg/mL. Cytotoxic activity of CHE on JHH-4 cells is characterized by an IC50 value of 16.62 μg/mL which is classified as having strong cytotoxic activity. This study concluded that CHE has the potential to be developed as a chemopreventive agent in liver cancer.Keywords: liver cancer, hepatocelullar carcinoma, Chemopreventive, antioxidant,Curcuma heyneana
Citrus sinensis Peel Extract Synergistically Enhances the Cytotoxic Effect of Chemotherapeutic Agents on HepG2 Cells
Full text linkDoxorubicin (DOX) and cisplatin (Cis), non-specific chemotherapeutic agents used for hepatocellular carcinoma (HCC), are frequently combined with synthetic or natural agents to enhance their cytotoxic effects. Citrus sinensis peel extract (CPE) serves as a natural source of flavonoids, including sinensetin (SIN), which has the potential to increase the efficacy of DOX and Cis. This study aimed to observe the effect of CPE and SIN one of CPE compounds, in enhancing liver cancer cell susceptibility to doxorubicin and cisplatin. The assays conducted in this study included a phytochemical analysis of CPE using TLC, cell viability assays against HepG2 cells using MTT assay in both single and combination forms, and cell viability assays on Vero cells. The result confirmed the presence of SIN as one of the compounds in CPE. Both CPE and SIN, when used individually, exhibited moderate cytotoxic effects on HepG2 cells with IC50 of 101.09 μg/mL and 83.13 μM, respectively, while showing no cytotoxic effect on Vero cells. Cis demonstrated significant cytotoxicity against HepG2 cells with an IC50 of 7.86 μM. DOX exerted a strong cytotoxic effect on both HepG2 and Vero cells, with the IC50 of 2.52 μM and 13.98 μM. It was observed that CPE was able to synergistically enhance the cytotoxic effects of DOX, and SIN synergistically increased the cytotoxicity of Cis, particularly against HepG2 cells, with CI<1.0.Keywords: CPE, SIN, Cisplatin, Doxorubicin, HCC
Molecular Docking and Molecular Dynamic Simulation on the Interaction of Saffron’s Active Compunds with HER-2 Protein
Full text linkHuman epidermal growth factor receptor-2 (HER-2) is an essential oncogene in breast cancer. HER-2 causes 25% of breast cancer, and this type of cancer tends to grow and spread faster than others but had a good response to HER-2 targeted therapy. This study aims to analyze chemical compounds in saffron plants (Crocus sativus) that potential to breast anticancer activity by inhibiting HER-2 receptor (PDB ID: 3RCD). The study employed in silico research such as molecular docking using AutoDock Tools software, and visualization with Biovia Discovery Studio. In addition, molecular dynamic simulation was conducted using GROMACS software, with visualization performed using Grace. The molecular docking results showed that Crocetin has a lower binding energy value of -8.37 kcal/mol compared to Herceptin, which is -7.11 kcal/mol and the lowest energy among Saffron bioactive compounds. These results indicated that the affinity of Crocetin in binding to HER-2 receptor is better than Herceptin. The molecular interactions were hydrogen, hydrophobic, electrostatic, and unfavorable bonds. The MD results showed that the RMSD value meets the 0.2-0.5 nm stability requirements. According to the data analysis, Herceptin appears to have a more stable RMSF value when compares to Crocetin. The Rg graph of both complexes showed stability until the end of the simulation. The H-bond results show that the Herceptin complex has more hydrogen bonds than the Crocetin complex. These results showed that the chemical components of saffron plants have the potential as breast anticancers by inhibiting the HER-2 receptor.Keywords: anticancer, Crocus sativus, HER-2 receptor, molecular docking, molecular dynamic
Ethanol Extract of Artocarpus odoratissimus (Tarap) Bark Inhibit Migration of MDA-MB-231 Triple Negative Breast Cancer Cells
Full text linkBreast cancer is the most diagnosed cancer in the world, with triple negative breast cancer (TNBC) being one of its subtypes that exhibits an aggressive clinical course, a tendency for early metastasis, and a poor prognosis. Tarap (Artocarpus odoratissimus Blanco) is an endemic plant of East Kalimantan, which possesses anticancer potential. This study aimed to explore the ability of ethanol extract of Tarap bark (EETB) in reducing cell viability, inducing apoptosis and inhibiting migration of MDA-MB-231 cells. Cell viability was observed by 3-(4.5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. EETB -induced apoptosis was analyzed by double staining allophycocyanin (APC) Annexin V with PI kit through flow cytometry. Cell migration was determined through scratch assay. EETB was found to decrease cell viability with an IC50 value of 1607.302 μg/ml (R=0.369). EETB’s ability to induce total apoptosis did not show significant differences across various concentrations. EETB was able to inhibit cell migration, especially at concentrations of 800 mg/ml, both at 24-h and 48-h observations. This finding demonstrates that EETB has a weak effect on reducing the viability and inducing the apoptosis of MDA-MB-231 cells. EETB induced morphological cells type change in to globular type and significantly inhibits two-dimensional migration of MDA-MB-231 cells.Keywords: Tarap, Artocarpus odoratissimus, triple negative breast cancer
Apoptosis Induction of SKOV-3 Ovarian Cancer Cells from Pacing Rhizome (Costus speciosus) Through the Modulation of BAX and P53 Genes Expression
Full text linkCostus speciosus or Pacing has been investigated to have cytotoxic effect on several human cancer cells. Current was conducted to determine the cytotoxic activity of ethanol extract of the Pacing rhizome (EP) on SKOV-3 ovarian cancer cells, to investigate EP’s effect on BAX and p53 expression, and predict the inhibition activity on intrinsic pathway. EP were extracted using maceration method with 70% ethanol. The cytotoxic effect was performed using MTT Assay with various concentrations (375 μg/mL, 250 μg/mL, 62.5 μg/mL, 31.25 μg/mL, and 7.8125 μg/mL). The ability of EP to induce apoptosis in SKOV-3 cells was measured using flow cytometry. The BAX and p53 gene expressions on SKOV-3 cells were detected with RT-qPCR after treatment of EP with concentrations of ¼ IC50, ½ IC50, and IC50. The ability of diosgenin to interact with BAX and p53 can be seen from the interaction with the MCL-1 protein and was predicted with molecular docking. The results showed that IC50 of cytotoxic activity was 69.143 μg/mL. EP could induce apoptosis on SKOV-3 cells and can induce BAX and p53 protein expressions. The docking results show that diosgenin has the potential to act as an antagonist for the MCL-1 protein, it can increase apoptosis.Keywords: apoptotic, Costus speciosus extract, SKOV-3, p53, BAX
Bioinformatics Analysis of Inhibition Activation SHP-2 by Galangal as Activating Agent of Cancer Immunotherapy
Full text linkInterleukin 12 (IL-12) is a pro-inflammatory cytokine type 1 that has acted as a potential immunotherapy for cancer. The mechanism of IL-12 increases the activity of cytotoxic T cells and Natural Killer (NK) cells, reverse tumor-induced immunosuppression, prevent angiogenesis, and increases lymphocyte and antigen transport. Galangal is one of the natural ingredients that have biological activity as an anticancer and immunomodulator. In this research, researchers wanted to know the potential of the active compound of galangal to activate IL-12 by inhibiting the IL-12 analog, namely SHP-2. This research uses bioinformatics studies using several databases such as RCSB PDB, ChEMBL, Dr. Duke's Phytochemical and Ethnobotanical, UALCAN, OncoLnc and computational analysis using KNIME and MOE software. The SHP-2 structure used is taken from the RCSB PDB with the code 5EHR. The 10 compounds with the highest predictions of inhibiting SHP2 using KNIME were obtained, then molecular docking was performed using MOE and three compounds that had the potential to inhibit SHP-2 were Kaempferide, Galangin, and RiboflavinKeywords: cancer, computing, galangal, Interleukin 12, SHP-2