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INDONESIA
Indonesian Journal of Cancer Chemoprevention
Published by Indonesian Society for Cancer Chemoprevention
ISSN : 23558989     EISSN : 20880197     DOI : -
Core Subject : Health, Science,
Biochemistry, Genetics & Molecular Biology Medicine & Pharmacology
Indonesian Journal of Cancer Chemoprevention (IJCC) is an open access, peer-reviewed, triannual journal devoted to publishing articles on Cancer Chemoprevention including Experimental and Clinical Pharmacology, especially concerning Anti-Oxidants, Anti-Aging, Anti-Inflammation, Anti-Angiogenesis, and Anti-Carcinogenesis; Cancer Detection; Stem Cell Biology; Immunology; in vitro and in silico Exploration of Chemopreventive Mechanism; and Natural Products.
Arjuna Subject : -
Articles 334 Documents
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Solanum nigrum Ethanolic Extract (SNE) Increases Cytotoxic Activity of Doxorubicin on MCF-7 Cell Dyaningtyas Dewi Pamungkas Putri; Erlina Rivanti; Raditya Prima Istiaji; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 12, No 2 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.
α-Mangosteen as An Oxidative Inhibitor in Hepatocellular Carcinoma Harliansyah Harliansyah; Nunung Ainur Rahmah; Kuslestari Kuslestari
Indonesian Journal of Cancer Chemoprevention Vol 12, No 2 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.
Inhibition of Human Epidermal Growth Factor Receptor-2 (HER-2) from Pomelo (Citrus maxima) Flavonoid Compounds: an In Silico Approach Roihatul Mutiah; Tanaya Jati Dharma Dewi; Arief Suryadinata; Kesimira Qonita
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.
Citrus Flavonoids from Citrus reticulata Peels Potentially Target an Autophagy Modulator, MAP1LC3A, in Breast Cancer Bayu Anggoro; Dennaya Kumara; Dhella Angelina; Muthi Ikawati
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.
Bioinformatics Analysis of Rho GTP-ase Activating Protein 35 (ARHGAP35) in Breast Cancer Migration Dicky Rizky Febrian; Joko Setyono; Muhamad Salman Fareza; Nur Amalia Choironi; Arif Fadlan; Sarmoko Sarmoko
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.
Association between Vitamin D and Calcium Level and BMD Alteration in Post-Menopausal Osteoporosis Patients Treated with Bisphosphonate Therapy for at Least 1 Year in Saiful Anwar Hospital Malang Hamzah Hamzah; Thomas Erwin Christian Junus Huwae; Chodidjah Chodidjah
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.
A Mini-Review: Possible Mechanisms of Hepatoprotective Effect of Aloe Vera Gel 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 Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.
Addition of Beetroot Extract to Neoadjuvant Adriamycin Cyclophosphamide Regimen Increased Tumor Cell Apoptosis in Mammary Adenocarcinoma Rats Sri Susilowati; Neni Susilaningsih; Catharina Suharti
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.
Phytochemical and Bioinformatic Studies of Citrus Flavonoids as Chemopreventive Agents Targeting GGPS1 for Liver Cancer Ratih Kurnia Wardani; I Made Rhamandana; Christina Mutiara Putri Gono; Muthi Ikawati
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.
Induction of Helianthus annuus Leaves Extract to HeLa cell Apoptosis and Cell Cycle Arrest in S, G2-M and M5 Phase Roihatul Mutiah; Jauza Ulfah; Muhammad Firman Amrulloh; Arief Suryadinata; Yen Yen Ari Indrawijaya; Ana Rahmawati
Indonesian Journal of Cancer Chemoprevention Vol 13, No 1 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 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.

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