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In-silico Study of Certain Phytoestrogen Flavonoids Involved in Breast Cancer by Evaluating their Comparative Binding Interaction with Human Estrogen Receptors (Erα and Erβ) to Identify Better Anti-estrogenic Activity
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Breast cancer is the most common cause of cancer deaths among women worldwide. Although estrogen is involved in the development of the mammary gland, hyper-estrogen can be carcinogenic. Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. In this molecular docking study, the binding of certain flavonoids and isoflavonoids viz., apigenin, genistein, kaempferol, and quercetin with the human Estrogen Receptor (ER) alpha and beta were analyzed. Apigenin showed high binding efficiency of -7.87 Kcal/ mol and -8.06Kcal/mol with ERα and ERβ, respectively, whereas kaempferol showed binding efficiency of -7.44Kcal/mol and -7.46Kcal/mol with ERα and ERβ, respectively. Quercetin showed binding efficiency of -7.57Kcal/mol and -7.89Kcal/ mol, while the isoflavonoid genistein showed low binding efficiency of -3.37Kcal/mol and -3.57Kcal/mol towards ERα and ERβ, respectively. Thus, apigenin, kaempferol, and quercetin revealed high binding efficiency with the human estrogen receptors alpha and beta, while genistein showed low binding efficiency towards both receptors. Hence, the consumption of different phytoestrogen-rich foods may help in the prevention and/or treatment of breast cancer, although further scientific investigations are required.
Keywords
Antiestrogenic, Apigenin, Breast Cancer, Docking, Genistein, Kaempferol, Phytoestrogens, Qercetin.
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- Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality world¬wide for 36 cancers in 185 countries. CA Cancer Journal for Clinicians. 2018; 68(6):394-424. https://doi.org/10.3322/caac.21492 PMID:30207593
- Secretan BL, Scoccianti C, Loomis D, et al. Breast cancer screening viewpoint of the IARC working group. New England Journal of Medicine. 2015; 372(24): 2358-8. https://doi.org/10.1056/NEJMsr1504363 PMID:26039523
- Paterni I, Carlotta GC, Katzenellenbogen JA, Minutoloa F. Estrogen receptors alpha (ERα) and beta (ERβ): Subtype selec¬tive ligands and clinical potential. Steroids. 2014; 90:13-29. https://doi.org/10.1016/j.steroids.2014.06.012 PMID:24971815 PMCID:PMC4192010
- Nikolic IL, Savic-Gajic IM, Tacic AD,Savic IM. Classification and biological activity of phytoestrogens: A review. Advanced Technologies. 2017; 6(2):96-106. https://doi.org/10.5937/savteh1702096N
- Jacquot Y, Rojas C, Refouvelet B, et al. Recent advances in the development of phytoestrogens and derivatives: An update of the promising perspectives in the prevention of postmenopausal diseases. Mini Reviews in Medicinal Chemistry. 2003; 3(5):387-400. https://doi.org/10.2174/1389557033488006 PMID:12769692
- Turktekin M, Konac E, Onen HI, et al. Evaluation of the effects of the flavonoid apigenin on apoptotic pathway gene expression on the colon cancer cell line (HT29). Journal of Medicinal Food. 2011; 14(10):1107-17. https://doi.org/10.1089/jmf.2010.0208 PMID:21548803
- Azevedo C, Branco AC, Araujo JR, et al. The chemopreventive effect of the dietary compound Kaempferol on the MCF-7 human breast cancer cell line is dependent on inhibition of glucose cellular uptake. Nutrition and Cancer. 2015; 67(3):504-13. https://doi. org/10.1080/01635581.2015.1002625 PMID:25719685
- Tsiklauri L, Anb G, Ruszaj DM, et al. Simultaneous determination of the flavonoids robinin and kaempferol in human breast cancer cells by liquid chromatography-tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. 2011; 55(1):109-13. https://doi.org/10.1016/j.jpba.2010.12.021 PMID:21232900
- Diantini A, Subarnas A, Lestari K, et al. Kaempferol-3-O-rhamnoside isolated from the leaves of SchimawallichiiKorth. inhibits MCF-7 breast cancer cell proliferation through activation of the caspase cascade pathway. Oncology Letters. 2012; 3(5):1069-1072. https://doi.org/10.3892/ol.2012.596 PMID:22783393 PMCID:PMC3389640
- Choi EJ, Ahn WS. Kaempferol induced the apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 cells. Nutrition Research and Practice. 2008; 2(4):322-5. https://doi.org/10.4162/nrp.2008.2.4.322 PMID:20016737 PMCID:PMC2788196
- Kim KY, Jang WY, Lee JY, et al. Kaempferol activates G2-checkpoint of the cell cycle resulting in G2-arrest and mitochondria-de¬pendent apoptosis in human acute leukemia Jurkat T cells. Journal of Microbiology and Biotechnology. 2016a; 26(2):287-94. https://doi.org/10.4014/jmb.1511.11054 PMID:26699757
- Kim SH, Hwang KA, Choi KC. Treatment with kaempferol suppresses breast cancer cell growth caused by estrogen and triclosan in cellular and xenograft breast cancer models. Journal of Nutritional Biochemistry. 2016b; 28:70-82. https://doi.org/10.1016/j. jnutbio.2015.09.027 PMID:26878784
- Chirumbolo S. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflammation and Allergy. 2010; 9(4):263-285. https://doi.org/10.2174/187152810793358741 PMID:20887269
- Li Y, Yao J, Han C, et al. Quercetin, inflammation and immunity. Nutrients. 2016; 8(3):167. https://doi.org/10.3390/nu8030167 PMID:26999194 PMCID:PMC4808895
- Lai WW, Hsu SC, Chueh FS, et al. Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signalling pathways. Anticancer Research. 2013; 33(5):1941-50.
- Chan CY, Lien CH, Lee MF, Huang CY. Quercetin suppresses cellular migration and invasion in human Head and Neck Squamous Cell Carcinoma (HNSCC). Biomedicine. 2016; 6(3):10-5. https://doi.org/10.7603/s40681-016-0015-3 PMID:27510965 PMCID:PMC4980310
- Yuan-Jing F, Nan-Shan H, Lian X. Genistein synergizes with RNA interference inhibiting surviving for inducing DU-145 of pros¬tate cancer cells to apoptosis. Cancer Letters. 2009; 284(2):189-97. https://doi.org/10.1016/j.canlet.2009.04.024 PMID:19433345
- Liu H, Du J, Hu C, et al. Delayed activation of extracellular-signal-regulated kinase ½ is involved in genistein- and equol-in¬duced cell proliferation and estrogen-receptor-alpha-mediated transcription in MCF-7 breast cancer cells. Journal of Nutritional Biochemistry. 2010; 21(5):390-6. https://doi.org/10.1016/j.jnutbio.2009.01.016 PMID:19427779
- Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer (Dove Med Press). 2019; 11:151-64. https://doi.org/10.2147/BCTT.S176070 PMID:31040712 PMCID:PMC6462164
- Zbiral B, Weber A, Iturri J, et al. Estrogen modulates epithelial breast cancer cell mechanics and cell-to-cell contacts. Materials (Basel). 2021; 14(11):2897. https://doi.org/10.3390/ma14112897 PMID:34071397 PMCID:PMC8198807
- Okoh MP, Singla RK, Madu C, et al. Phytomedicine in disease management: In-silico analysis of the binding affinity of artesunate and azadirachtin for malaria treatment. Frontiers in Pharmacology. 2021; 12:751032. https://doi.org/10.3389/fphar.2021.751032 PMID:34916935 PMCID:PMC8669099
- Lee Y, Lee J, Lim C. Anticancer activity of flavonoids accompanied by redox state modulation and the potential for a chemother-apeutic strategy. Food Science Biotechnology. 2021; 30(3):e321-40. https://doi.org/10.1007/s10068-021-00899-8 PMID:33868744 PMCID:PMC8017064
- Rickard DJ, Monroe DG, Ruesink TJ, et al. Phytoestrogen genistein acts as an estrogen agonist on human osteoblastic cells through estrogen receptors α and β. Journal of Cellular Biochemistry. 2003; 89(3):633-646. https://doi.org/10.1002/jcb.10539 PMID:12761896.
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