ISCC Indonesian Journal of Cancer Chemoprevention最新文献

{"title":"Induction of Helianthus annuus Leaves Extract to HeLa cell Apoptosis and Cell Cycle Arrest in S, G2-M and M5 Phase","authors":"R. Mutiah, Jauza Ulfah, Muhammad Firman Amrulloh, Arief Suryadinata, Yen yen Ari Indrawijaya, Ana Rahmawati","doi":"10.14499/indonesianjcanchemoprev13iss1pp1-11","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp1-11","url":null,"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.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79994712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Study of Chemical Compounds in Plantago major L. as Anti-Androgen","authors":"A. Baihaqi, Hasna Siti Munifah Isman, Ganis Fitria Fauziyyah, Rismauli Ruth Natasari Hutabarat, Adi Hartono, S. Megantara","doi":"10.14499/indonesianjcanchemoprev13iss1pp33-45","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp33-45","url":null,"abstract":"Prostate cancer is the most common type of cancer diagnosed in men worldwide and the second leading cause of death after lung cancer. Testosterone and dihydrotestosterone (DHT) have been known to play an essential role in prostate cancer. Androgen receptor (AR) binding to the ligand allows homodimerization and translocation to the nucleus, which acts as a transcription factor for androgen-responsive genes such as PSA (Prostate-specific antigen). Although many anti-androgens have been established, including Bicalutamide, Flutamide, and Abiraterone, the problem of non-specific cytotoxicity effects and cancer recurrence due to potential drug resistance remains a significant obstacle to establishing effective therapy. Plantago major L. is one of the plants that can choose anticancer therapy because, based on reports, it has anticancer activity through DNA damage in cancer cells. This study focused on the search for the potential phytochemical activity of Plantago major L. as an anti-androgen, non-cytotoxic, and had significant AR inhibitory activity. This study uses Lipinski prediction (RO5), ADMET prediction, and a structure-based approach with molecular docking techniques using the PDB ID 2AM9 receptor structure and 13 compounds from Plantago major L. as test ligands compared to known AR antagonists. From the research results, Hispidulin has the highest potential as an anti-androgen with binding energy (-9.43 kcal/mol) that is closest to natural ligands and is smaller than Flutamide as a comparison drug. This anti-androgen activity was hypothesized from the similarity of hydrogen bonds with amino acid residues 705-Asn and 711-Gln as key AR residues present in Hispidulin.Keywords: Prostate cancer, Androgen Receptor, Plantago major L., ADMET, In Silico.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86762642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Curcuma, a Powerful Epigenome Modulator in Breast Cancer: an In Silico Study","authors":"Amel Elbasyouni, L. Saadi, AbdelKarim Baha","doi":"10.14499/indonesianjcanchemoprev13iss1pp61-70","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp61-70","url":null,"abstract":"The inhibition of DNA methyltransferase-1 enzyme can strongly decrease the capacity of cells to enhance the tumour-genesis process. Members of the Estrogen-Related Receptors family regulate several elements of cellular metabolism. These are orphan nuclear receptors that regulate a wide range of functional gene networks involved in breast carcinogenesis and the regulation of associated methionine and folate cycles, providing a proven direct relationship to DNA methylation as a result. Moreover, dietary phytochemicals, such as Curcumin, can involve epigenetic modification, which may decrease the development of many types of cancer, especially breast cancer in women. We conducted this study to investigate the effect of Curcuma (PubChem ID: 969516) on the epigenetic modification and inhibition of the DNA methyltransferase-1 (PDB ID: 3PTA) activity and Estrogen-Related Receptors (PDB ID: 1XB7) using Molecular docking approach and computational tools that may inform whether the Curcuma could provide this protective anticancer effect or not. Interestingly, the DNA methyltrasferase1-Curcumin and Estrogen-Related Receptors-Curcumin complexes display a docking score of -6.9 and -7.1 kcal/mol, respectively. Furthermore, Curcumin displays hydrogen, Pi-Cation, Pi-Anion and Van der Waals bonds with active site residues of the targeted molecules. By targeting DNA methylation via the combined inhibition of estrogen-related receptors and DNMT1, our research opens up a new therapeutic path for breast cancer treatment.Keywords: curcumin, breast cancer, epigenetic, molecular docking, treatment.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83714815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-protein Docking Studies of Estrogen Receptor Alpha and TRIM56 Interaction for Breast Cancer Drug Screening","authors":"B. A. Dhiani, N. Nurulita, F. Fitriyani","doi":"10.14499/indonesianjcanchemoprev13iss1pp46-54","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp46-54","url":null,"abstract":"Breast cancer is the highest mortality cause in women with cancer. Protein-protein docking for target-based screening is an effective approach in breast cancer drug discovery via estrogen receptor (ER) signaling. TRIM56, an E3 ubiquitin protein ligase, can bind to and stabilize ER alpha. Thus, drug screening that can inhibit or weaken the interaction between ER alpha and TRIM56 is promising to obtain novel yet specific breast cancer drugs. In this study, we performed protein-protein docking studies for ER alpha and TRIM56 interaction and virtual screening for FDA-approved drugs from the ZINC database against ER alpha and TRIM56 complex protein model structure. We utilized Cluspro 2.0, PyRx 0.8, and Pymol 2.4.1 to conduct protein-protein docking, virtual screening, and model structure visualization. PIP and PLIP software were also applied to analyze the amino acid residue between proteins or protein-ligands. Based on the protein-protein docking, ER alpha and TRIM56 established interaction. Utilizing this complex protein as a macromolecule in the virtual screen of 1071 molecules of FDA-approved drugs, we obtain the top five lowest binding energy molecules i.e., dutasteride, dihydroergotamine, nilotinib, ergotamine, and bromocriptine. In addition, the energy binding affinity between ER alpha-dutasteride complex with TRIM56 was weakened in the presence of dutasteride. In conclusion, protein-protein docking between ER alpha-TRIM56 was able to select FDA-approved drugs that could bind to the complex, and dutasteride binding to ER alpha-TRIM56 complex weakened the interaction.Keywords: protein-protein docking, estrogen receptor alpha, TRIM56, breast cancer, ubiquitin.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74147662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative activity of Ethanolic Extract of Kembang Bulan (Tithonia diversifolia) Leaf on HeLa Cervical Cancer Cell Line","authors":"E. Puspitasari, N. Nuri, I. Y. Ningsih, Bawon Triatmoko, Dewi Dianasari","doi":"10.14499/indonesianjcanchemoprev13iss1pp55-60","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp55-60","url":null,"abstract":"Tithonia diversifolia has been showed to be cytotoxic and antiproliferative on colon cancer, glioblastoma, hepatoma, kidney cancer, breast cancer, lung cancer, melanoma, leukemia, ovary cancer, prostate cancer, and stomach cancer cell lines, but not on cervical cancer cells yet. Our research aimed to determine the cytotoxicity and antiproliferative activity of T.diversifolia leaf ethanolic extract on HeLa cervical cancer cell line. The cytotoxicity and the antiproferative activity assay were done using MTT method for 24 h for cytotoxic assay; and series of 24, 48, and 72 h for antiproliferative assay. The cytotoxic activity was analyzed using IC50, while the antiproliferative assay was analyzed based on the proliferation kinetics. All assays were done in triplicate. T.diversifolia leaf ethanolic extract exhibited strong cytotoxic activity on HeLa cervical cancer cell lines with the IC50 of 97.839±10.120 μg/mL. The cytotoxic activity was dose dependent. Based on the proliferation assay, the antiproliferative activity was stronger as the incubation time and the dose increases. T.diversifolia leaf ethanolic extract showed strong cytotoxic and antiproliferative activity on HeLa cervical cancer cell lines.Keywords: T.diversifolia leaf ethanolic extract, cytotoxicity assay, antiproliferative assay, HeLa cervical cancer cells.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74935124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effectiveness of Topical 5-fluorouracil Treatment on Mouse Skin Squamous Cell Precancerous Lesions through Caspase-3 Expression","authors":"Siti Nurkasanah, A. Hoemardani, E. S. Sinuraya, P. Wuyung","doi":"10.14499/indonesianjcanchemoprev13iss1pp12-21","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp12-21","url":null,"abstract":"Skin cancer is a disease that develops in the epidermis of the skin and can be invasive, such as squamous cell carcinoma (SCC). Early detection of squamous cell precancerous can prevent these lesions from progressing to invasive SCC and increase the effectiveness of therapy. 5-fluorouracil (5-FU) is an antimetabolite compound as a pyrimidine DNA/RNA antagonist molecule that induces cell apoptosis. The main objective of this study was to evaluate the effectiveness of the topical 5-FU cream (Dharmais NCH) compared to imiquimod 5% on apoptosis through the expression of caspase-3 in precancerous squamous cells of mouse skin induced by 7,12-dimethylbenzen[a]-anthracene (DMBA)/croton oil treatment. This research assess three differences concentration of 5-FU include 1%, 2%, and 5% on 24 wild type mouse divided into 6 groups including positive control (with carcinogenesis but without treatment), negative control (without treatment; normal), carcinogenesis with treatment 5-FU cream (1%, 2%, and 5%) or 5% imiquimod cream. Two-stages carcinogenesis induced by DMBA and followed by croton oil. The expression of caspase-3 was analyzed using immunohistochemistry. Statistical analysis was performed by one-way ANOVA using SPSS version 23. The induction of two-stages of carcinogenesis (weeks 1 to 10) caused papilloma lesions on the skin of mouse. Furthermore, 5-FU treatment for 4 weeks (weeks 11 to 14) showed a decrease in the cumulative number of papillomas (p<0.05) and immunohistochemical analysis showed caspase-3 expression on 5-FU treatments (1%, 2%, and 5%) was not significantly different from the imiquimod treatment (p>0.05). The apoptotic effect of 5-FU treatment on precancerous skin squamous cell lesions in mouse was not significantly different from the standard treatment using imiquimod. This suggests that 5-FU treatment has potential as a future therapy in squamous cell precancerous skin lesions.Keywords: 5-fluorouracil, caspase-3, squamous cell precancerous, skin, topical treatment.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86218898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the Potential of Compounds in Sappan Wood as Cervical Cancer Metastasis Chemopreventive Agent With MMP9 Target","authors":"Hanaan Emilia Adi Hastuti, Midori Rahmadhany Putri Adisusilo, Yusufia Asmarani Ashar, E. Meiyanto, R. Jenie","doi":"10.14499/indonesianjcanchemoprev13iss1pp22-32","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev13iss1pp22-32","url":null,"abstract":"Matrix metalloproteinase-9 (MMP9) has an essential role in cervical cancer metastasis. Sappan wood extract (SWE) from Caesalpinia sappan contains metabolites that have pharmacological effects and can potentially inhibit metastasis by targeting the protein markers. This research aims to discover the potency of compounds in C. sappan as chemopreventive agents for metastasis in cervical cancer by targeting MMP9. SWE was obtained by maceration with methanol and analyzed using thin layer chromatography (TLC). In vitro cytotoxicity test of SWE on HeLa cells was performed by direct counting method. MMP9 expression profiles and survival rates in cervical cancer patients were explored through bioinformatics studies by the GEPIA database. The CMAUP and PubChem databases were used to obtain the metabolomic profile of SWE. SWE compounds’ activities on target proteins were obtained through KNIME software, while its interaction with MMP9 was analyzed using molecular docking with MOE software. We obtained SWE with a yield of 9.7% w/w. The extract contains brazilin and is indicated by the spot appearance at Rf 0.375. The cytotoxicity of SWE against HeLa cells was considered potential as the IC50 value was 54.93 μg/mL. Based on the bioinformatics analysis, there is a significant difference in MMP9 expression between normal and cervical cancer tissue. The patient’s survival probability decreased if MMP9 was overexpressed. The molecular docking results showed that active compounds of SWE bind to the MMP9 inhibition site with higher affinity compared to the native ligand. This study reveals that SWE potential to be developed as a chemopreventive agent through metastasis inhibition in cervical cancer by targeting MMP9.Keywords: Caesalpinia sappan L., metastasis, bioinformatics, molecular docking, MOE.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79872136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics Analysis of Rho GTP-ase Activating Protein 35 (ARHGAP35) in Breast Cancer Migration","authors":"Dicky Rizky Febrian, Joko Setyono, M. S. Fareza, N. Choironi, A. Fadlan, Sarmoko Sarmoko","doi":"10.14499/indonesianjcanchemoprev12iss3pp161-169","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp161-169","url":null,"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.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81860287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addition of Beetroot Extract to Neoadjuvant Adriamycin Cyclophosphamide Regimen Increased Tumor Cell Apoptosis in Mammary Adenocarcinoma Rats","authors":"S. Susilowati, N. Susilaningsih, C. Suharti","doi":"10.14499/indonesianjcanchemoprev12iss3pp130-136","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp130-136","url":null,"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.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81194253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Citrus Flavonoids from Citrus reticulata Peels Potentially Target an Autophagy Modulator, MAP1LC3A, in Breast Cancer","authors":"B. Anggoro, Dennaya Kumara, Dhella Angelina, Muthi’ Ikawati","doi":"10.14499/indonesianjcanchemoprev12iss3pp114-122","DOIUrl":"https://doi.org/10.14499/indonesianjcanchemoprev12iss3pp114-122","url":null,"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.","PeriodicalId":32620,"journal":{"name":"ISCC Indonesian Journal of Cancer Chemoprevention","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89893652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}