Indonesian Journal of Cancer Chemoprevention
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Bioinformatic and Molecular Docking Study of Zerumbone and Its Derivates against Colorectal Cancer
Full text linkThe prevalence of colorectal cancer (CRC) is ranked third among all cancer types in both men and women, highlighting the urgency for drug exploration. Zerumbone and its derivatives have gained attention for their ability to inhibit angiogenesis, invasion, and metastasis and have been tested for their efficacy against various cancer cells. This study aimed to investigate the potential targets and mechanism of action of zerumbone derivatives in colon cancer invasion and migration. Bioinformatic analysis was conducted using STITCH and STRING to identify potential target genes, and molecular docking was used to search for anticancer candidates from 20 zerumbone derivatives. The results revealed that six proteins were targeted by zerumbone derivatives, including XIAPBIR3 (1TFT), AKT1 (3O96), JAK2 (6VGL), HASP90AA (2XJX), MDM2 (4MDN), and XIAPBIR2 (4KJU). Compound 4 was found to have a lower binding energy than zerumbone as well as AZD5363 (pan-Akt inhibitor) when interacting with the protein target AKT1. This makes it the most promising candidate among the zerumbone derivatives for treating colorectal cancer. Further development, such as the addition of an amine functional group, is expected to improve the potency of this molecule through the formation of hydrogen bonds and other interactions with lower bond energy.Keywords: Bioinformatic, molecular docking, zerumbone derivatives, colorectal cancer
Effect of Astaxanthin Supplementation in Preventing Anemia in Head and Neck Cancer Patients Receiving Cisplatin Chemotherapy
Full text linkThe incidence of anemia due to reactive oxygen species (ROS) in patients with head and neck cancer (HNC) can be caused by a side effect of cisplatin chemotherapy, namely myelosuppression. In the presence of ROS, external antioxidants are needed, including astaxanthin as an antioxidant to neutralize and fight ROS in preventing anemia. This study aims to prove and analyze the antioxidant effect of astaxanthin in preventing anemia in HNC patients due to cisplatin chemotherapy for 3 weeks. The study design was a randomized controlled trial pre-post test design, involving 42 research subjects who were randomly divided into two groups, then 3 cc of blood was taken I to check the hemoglobin level and the number of erythrocytes. The treatment group was given astaxanthin 2x4 mg and the control group was given a combination of vitamin C 1x500 mg and vitamin E 1x250 IU for 3 weeks then 3 cc of blood was taken II to check hemoglobin levels and erythrocyte counts. The independent variable is intake of astaxanthin, the dependent variable is hemoglobin level and the number of erythrocytes and the confounding variables are age, sex, type of HNC, stage of HNC, ECOG and BMI. Data analysis was performed by the Descriptive test, Levene test, Shapiro Wilks, Wilcoxon test, and Mann-Whitney test. The significance of the hypothesis test was obtained with p<0.05. The 42 research subjects met the inclusion criteria, most aged between 41-50 years, male and female ratio 2:1, The most HNC were Nasopharyngeal Cancer, the most HNC stage was stage IV, the most HNC performance status was ECOG I and the most HNC patients had normal BMI. There was a significant difference in hemoglobin levels p=0.012 (p<0.05) and the number of erythrocytes, p=0.04 (p<0.05) between the treatment and control groups. There was a significant difference in hemoglobin levels after therapy in the treatment and control groups p=0.012 (p<0.05) and the number of erythrocytes p=0.04 (p<0.05) between the treatment and control groups. Astaxanthin can prevent anemia in the form of decreased hemoglobin levels and the number of erythrocytes in HNC patients who receive cisplatin chemotherapy.Keywords: astaxanthin, anemia, HNC, cisplatin, ROS
The Role of Serum IL-23 and Volatile Organic Compound Levels to RECIST 1.1 in The Evaluation of Therapeutic Response in Lung Cancer
Full text linkThe Response Evaluation Criteria in Solid Tumors (RECIST 1.1) is the gold standard for the assessment of lung cancer progression. However, the assessment and diagnosis of early treatment failure is challenging due to the limitations of current tools, as well as the long intervals and unavoidable side effects.This study aims to correlate volatile organic compound (VOC) patterns, serum level of interleukin-23 (IL-23), and RECIST 1.1 to assess chemotherapy response in lung cancer patients at Saiful Anwar Hospital. A prospective observational study was performed to 47 lung cancer patients who received three cycles of platinum-based chemotherapy. Using the Breath Analyzer to measure certain volatile organic compounds (VOCs), the study observed that three of the seven VOCs examined, formaldehyde (CH2O), toluene (C7H8), and hexane (C6H14), showed lower levels after three cycles of chemotherapy. Furthermore, there was a negative correlation between RECIST1.1 and acetone (C3H6O) (p=0.023), while RECIST1.1 and methane (CH4) had a positive correlation (p=0.011). Moreover, a significant positive correlation was observed between IL-23 after-chemotherapy and RECIST 1.1 (p=0.000). According to this study, a correlation exists between methane, IL-23, and RECIST 1.1 after three cycles of chemotherapy. The increase in methane and IL-23 aligns with the disease progression determined by RECIST 1.1. Furthermore, The decrease in acetone after chemotherapy showed a negative correlation with RECIST1.1, consistent with disease progression.Keywords: Volatile Organic Compound, Interleukin-23, RECIST 1.1
Impact of Donor Age on Human Platelet Lysate Quality and its Consequential Effects on HeLa Cell Growth in the Presence of Anti-Cancer Compounds
Full text linkAn integral aspect of anticancer experimentation involves delineating the optimal dosage of the test compound to ascertain its efficacy in targeting malignant cells. Numerous variables may influence a compound's cytotoxicity, among which is the choice of cell culture medium. Within in vitro settings, supplementary mediums are employed to foster cellular proliferation. Platelet lysate (PL) serves as a growth supplement, presenting an alternative to fetal bovine serum (FBS), primarily due to its incorporation of growth factors such as platelet-derived growth factor (PDGF), a component absents in FBS. The integrity of PL may be subject to various factors, including the age of the donor. This study sought to evaluate the impact of donor age on PL quality. Furthermore, it aimed to discern whether PL derived from platelet concentrate (PC) blood components of different age cohorts influences the IC50 value in anticancer compound assessment. Expired PCs were utilized, subsequently classified into age categories: ≤30 years, >30 years, and a combination of ages. PL analysis encompassed parameters such as pH, blood profile, protein, glucose, and cholesterol levels. The investigation scrutinized the influence of PL quality, as a cellular growth supplement, on the anticancer compound cisplatin's activity against HeLa cells. Findings indicate that donor age influenced the IC50 value of cisplatin on HeLa cells. Notably, elevated cholesterol levels and decreased pH in PL from donor ages >30 years were associated with reduced cisplatin toxicity.Keywords: Cisplatin, Donor Age, HeLa, IC50, Platelet Lysate
Activity of Ethanol Fraction Melinjo (Gnetum Gnemon L.) Seed on Colonic Cancer (Widr) Cells as Co-Chemotherapy Agent
Full text linkCancer deaths increase every year, including in Indonesia. The low selectivity of chemotherapy agents and the resistance of cancer cells against chemotherapy agents is the main cause of chemotherapy treatment failure. It causes serious side effects in sufferers. Beside that, plants produce secondary metabolites which are being investigated for the anticancer activity that is used as new clinical drugs. Therefore we need research that uses plants as co-chemotherapy agents. Melinjo seeds (Gnetum gnemon L.) contain gnetin C has the potential to apoptosis WiDr colon cancer cells. The purpose of this study was to determine the potential of Ethanol Fraction Melinjo Seed (EFMS) as a co-chemotherapy agent for colon cancer. The sample was maceration using 70% ethanol and fractionated with ethanol. Phytochemical screening with thin layer chromatography (TLC)-Densitometry, antioxidant test used the DPPH, while the cytotoxic activity of WiDr colon cancer cells and their combination with 5-Fluorouracil chemotherapy agent using the 3-(4,-5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide (MTT) Assay, and also in silico test used molecular docking between gnetin C on EFMS and IKK and COX-2 proteins with the 5-FU. The results showed that EFMS contains gnetin C based on Rf value, has weak antioxidant activity with IC50 1227 μg/mL, weak cytotoxic activity in WiDr colon cancer cells with IC50 681 μg/mL and has combined activity synergistic with 5-Fluorouracil. Molecular docking showed gnetin C strong binding affinity against IKK and COX-2 proteins with scores -12.2 kcal/mol and -9.6 kcal/mol. The result concludes that EFMS has the potential to inhibit the development of cancer cells, especially WiDr colon cancer cells.Keywords: Gnetum gnemon L., Colon Cancer, Cytotoxic, Molecular docking, WiDr
Distribution and Viability of Peripheral Blood Mononuclear Cells from Imatinib-resistant Chronic Myeloid Leukemia Patients: an In Vitro Study
Full text linkThe incidence of Chronic Myeloid Leukemia (CML) in the world is approximately 1.5 cases per 100,000 individuals. The level of resistance to CML treatment, imatinib in Indonesia is relatively high compared to Europe. Culturing CML cells can be used as a model for the determination of pathogenesis of CML, drug efficacy testing, and drug resistance testing. Studies using CML patients’ cells to be cultured in vitro and the methods used are rarely varied. This study aims to examine the distribution and viability of peripheral blood mononuclear cells from imatinib-resistant CML patients, expected to be a reference for mononuclear cell cultures from CML patients. This study was conducted in June-August 2019 using quantitative descriptive methods. The sample was mononuclear cells isolated from peripheral blood of three imatinib-resistant CML patients at the Hemato-Oncology Polyclinic of Hasan Sadikin Hospital, each of which was cultured in vitro using RPMI 1640 for 28 days. Distribution were seen using Giemsa staining, while viability was calculated using trypan blue. Data is processed using Microsoft Excel 2013 and Graphpad. Cell viability decreased during culture. Cell distribution had a different development pattern. Blast cells, eosinophils and basophils had presentation of between 0-5%. The percentage of lymphocyte changed between 11-31%. The percentage of neutrophil changed between 16-41%. The percentage of immature cells decreased, whereas the percentage of monocyte increased. In conclusion, cell viability decreases during the culture. Distribution of cells similar to the initial condition lasted until the 7th day and in the final phase it was only dominated by monocytes.Keywords: myeloid leukemia, chronic, cell culture, in vitro, peripheral blood mononuclear cell, cell viability
Cytotoxic and Anti-proliferative Effects of Ethanol Extract of Marine Sponge Stylissa carteri on Colon Cancer HCT-116 Cell Line
Full text linkColorectal cancer is one of the most diagnosed cancers in the world. KRAS mutations in colon cancer are being responsible for the progressiveness and resistance of the standard therapeutic available. Marine sponge is one the sources for chemotherapy. Stylissa carteri is a marine sponge that lives in Indonesia and its anti-cancer effects are starting to be explored nowadays. The purpose of this study was to determine the cytotoxicity and anti-proliferative effect of ethanol extract of Stylissa carteri against colon cancer cells with KRAS mutations HCT-116 cells. This was an in vitro study using colon cancer cell line HCT-116 which was tested by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue assay. The trypan blue assay was performed on control and treated cells at 72 h. The MTT assay was performed on cells which were previously incubated with Stylissa carteri extract. Sponge Stylissa carteri was taken from Pramuka island, Taman Nasional Kepulauan Seribu, Jakarta. The IC50 of ethanol extract of Stylissa carteri is 5 μg/mL (R square 0.9550) in HCT-116 cells. The trypan blue assay showed doubling time of incubated cell for 48 h was 26.10 h for control and 39.69 h for treated cells, respectively. Ethanol extract of Stylissa carteri has cytotoxic and anti-proliferative effects in HCT-116 colon cancer cells with KRAS mutation.Keywords: Colon Cancer, HCT-116, KRAS Mutation, Marine Sponge, Stylissa carteri
Etlingera elatior Compounds as Anticancer Agents of Breast Cancer Through Inhibition of Progesterone Receptor: An In Silico Study
Full text linkBreast cancer is the leading cause of cancer-related death in women globally. Progesterone receptor (PR) is known as the prime example of receptors amenable to targeted breast cancer drug therapy. Etlingera elatior is an herbal plant that has been renowned to have anticancer effect. This study aimed to identify the potential compounds derived from Etlingera elatior as anticancer agents of PR in breast cancer using molecular docking method. This study used fifteen compounds from Etlingera elatior along with lonaprisan as the comparative drug. The PR was downloaded from RCSB, whereas compounds and lonaprisan were from Pubchem. The drug-likeness test based on Lipinski’s rule of five was conducted using SwissADME. Toxicity analysis using admetSAR 2.0 was used to predict toxicological profile of the compounds. Compounds and lonaprisan were docked on PR using AutoDock tools 1.5.6 and AutoDock Vina 1.1.2. Molecular interactions were visualized by Discovery Studio v16. A total of nine compounds met the criteria as drugs based on drug-likeness and toxicity tests. All nine compounds except caffeic acid and vanillic acid had higher binding affinities on PR compared with lonaprisan. Ergosterol peroxide exhibited the highest binding affinity on PR with values of -9.8 kcal/mol. Moreover, ergosterol peroxide-PR interaction had thirteen hydrophobic bonds and a hydrogen bond with amino acid residues were found in the active site of PR. Most of the compounds found in Etlingera elatior have the potential to be anticancer agents of PR in breast cancer with ergosterol peroxide being the most potential compound. Further in vitro and in vivo research are needed.Keywords: breast cancer, ergosterol peroxide, Etlingera elatior, progesterone receptor, in silico
In Silico and In Vitro Study Selaginella doederleinii Herb Extract as An Antineoplastic on MCF-7 Cells and Formulation Development of Nano Effervescent Granule
Full text linkBreast cancer, the leading cause of cancer-related deaths in women with 685,000 deaths in 2020. Exploring natural compounds with minimal side effects has emerged as a potential treatment. However, utilizing natural substances faces challenges, such as poor bioavailability, requiring technologies like nanotechnology to enhance absorption. This study focuses on evaluating Ethanol Extract of Selaginella doederleinii (EESD) as an anticancer against MCF-7, both in silico, in vitro methode and develop a formulation of EESD nanoparticle effervescent granules. This study commenced with extraction, Gas Chromatography-Mass Spectrometry (GC-MS) identification, in silico studies, namely bioinformatics and molecular docking, 3-(4,-5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide (MTT) Assay tests on MCF-7, and the formulation of nanoparticle preparations. EESD was extracted using the maceration method, resulting in an extract weighing 103.5 grams with a 6.9% yield. GC-MS identified three major compounds—cyclopentadecanoic, 2-hydroxy; hexadecanoic acid; and 9-octadecanoid, methyl ester. Bioinformatics revealed interactions with specific protein targets, and molecular docking indicated hexadecanoic acid's superior binding to TP53, surpassing paclitaxel at -8.7 kcal/mol. This suggests its potential to modulate TP53, impacting P53's role in impeding cancer cell growth. EESD exhibited an IC50 of 215μg/mL, signifying moderate cytotoxicity. In formulating nanoparticle effervescent granules, five formulas were transformed into nanoparticles and underwent organoleptic, pH, granule dissolution, and water content evaluations. Formula I is the formula that best meets the criteria with a pH of 6.55, granule dissolution <5 minutes, and water content <4%. The research results indicate that EESD shows anticancer activity against MCF-7 and this study has successfully developed a formula of nanoparticle from EESD in effervescent granule form.Keywords: Selaginella doederleinii, breast cancer, co-Cemotheraphy, MCF-7 Cell, in silico
Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with Cisplatin
Full text linkCisplatin (Cisp) is a non-specific chemotherapeutic agent for breast cancer. Hesperetin (HST), a flavanone found in various citrus fruits, exhibits bioactive properties, functioning as an antioxidant, anti-inflammatory, and anticancer agent. The objective of this research was to investigate the potential of HST as a co-chemotherapeutic agent in conjunction with Cisp, specifically focusing on its cytotoxic effects against 4T1 triple-negative breast cancer cells and senescence modulatory effect on Vero normal kidney cells. The cytotoxic effect and viability cell of HST were evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. In addition, the effect of cellular senescence inhibition on the Vero cell line was measured using senescence-associated β-galactosidase (SA-β-gal) staining. In the MTT assay, both HST and cisplatin demonstrated a reduction in the viability of 4T1 cells in a dose-dependent manner, yielding IC50 values of 498 μM and 2 μM, respectively. The co-treatment of HST and cisplatin showed an increase in sensitivity of the 4T1 cells with a combination index of <1. HST showed low cytotoxic activity against Vero cells, with IC50 values of over 500 μM. HST decreased cellular senescence induced by cisplatin exposure on Vero cells. These results indicated that HST in co-treatment with cisplatin decreased 4T1 cell viability synergistically. HST independently reduces the cellular senescence of normal cells. Consequently, HST holds promise for potential development as a co-treatment agent in combination with cisplatin for breast cancer cells, and it may also serve as an alternative for counteracting senescence in healthy tissues.Keywords: cytotoxic, senescence, hesperetin, cisplatin, breast cancer