{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:07:22Z","timestamp":1789697242398,"version":"4.0.1"},"reference-count":126,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Plant-derived compounds have recently attracted greater interest in the field of new therapeutic agent development. These compounds have been widely screened for their pharmacological effects. Polyphenols, such as soy-derived isoflavones, also called phytoestrogens, have been extensively studied due to their ability to inhibit carcinogenesis. These compounds are chemically similar to 17\u03b2-estradiol, and mimic the binding of estrogens to its receptors, exerting estrogenic effects in target organs. Genistein is an isoflavone derived from soy-rich products and accounts for about 60% of total isoflavones found in soybeans. Genistein has been reported to exhibit several biological effects, such as anti-tumor activity (inhibition of cell proliferation, regulation of the cell cycle, induction of apoptosis), improvement of glucose metabolism, impairment of angiogenesis in both hormone-related and hormone-unrelated cancer cells, reduction of peri-menopausal and postmenopausal hot flashes, and modulation of antioxidant effects. Additionally, epidemiological and clinical studies have reported health benefits of genistein in many chronic diseases, such as cardiovascular disease, diabetes, and osteoporosis, and aid in the amelioration of typical menopausal symptoms, such as anxiety and depression. Although the biological effects are promising, certain limitations, such as low bioavailability, biological estrogenic activity, and effects on target organs, have limited the clinical applications of genistein to some extent. Moreover, studies report that modification of its molecular structure may eliminate the biological estrogenic activity and its effects on target organs. In this review, we summarize the potential benefits of genistein on menopause symptoms and menopause-related diseases like cardiovascular, osteoporosis, obesity, diabetes, anxiety, depression, and breast cancer.<\/jats:p>","DOI":"10.3390\/molecules24213892","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T05:18:26Z","timestamp":1572499106000},"page":"3892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":162,"title":["Genistein as Potential Therapeutic Candidate for Menopausal Symptoms and Other Related Diseases"],"prefix":"10.3390","volume":"24","author":[{"given":"Prakash","family":"Thangavel","sequence":"first","affiliation":[{"name":"Programa de Posgrado en Neuroetolog\u00eda, Instituto de Neuroetolog\u00eda, Universidad Veracruzana, Av. Dr. Luis Castelazo Ayala s\/n, Col. Industrial \u00c1nimas, Xalapa C.P. 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-0210","authenticated-orcid":false,"given":"Abraham","family":"Puga-Olgu\u00edn","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Instituto de Neuroetolog\u00eda, Universidad Veracruzana, Av. Dr. Luis Castelazo Ayala s\/n, Col. Industrial \u00c1nimas, Xalapa C.P. 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5837-103X","authenticated-orcid":false,"given":"Juan F.","family":"Rodr\u00edguez-Landa","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Instituto de Neuroetolog\u00eda, Universidad Veracruzana, Av. Dr. Luis Castelazo Ayala s\/n, Col. Industrial \u00c1nimas, Xalapa C.P. 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-1141","authenticated-orcid":false,"given":"Rossana C.","family":"Zepeda","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biom\u00e9dicas, Universidad Veracruzana, Av. Dr. Luis Castelazo Ayala s\/n, Col. Industrial \u00c1nimas, Xalapa C.P. 91190, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.fertnstert.2013.05.005","article-title":"Adipokines, adiposity, and vasomotor symptoms during the menopause transition: Findings from the Study of Women\u2019s Health Across the Nation","volume":"100","author":"Thurston","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_2","first-page":"6","article-title":"Obesity is related to increased menopausal symptoms among Spanish women","volume":"16","author":"Cuadros","year":"2010","journal-title":"Menopause Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s40520-018-1109-4","article-title":"Executive summary of European guidance for the diagnosis and management of osteoporosis in postmenopausal women","volume":"31","author":"Kanis","year":"2019","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1080\/13697137.2018.1450855","article-title":"Postmenopausal endometriosis: Drawing a clearer clinical picture","volume":"21","author":"Tan","year":"2018","journal-title":"Climacteric"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.maturitas.2015.04.009","article-title":"EMAS position statement: Non-hormonal management of menopausal vasomotor symptoms","volume":"81","author":"Mintziori","year":"2015","journal-title":"Maturitas"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1001\/jama.2016.8012","article-title":"Use of Plant-Based Therapies and Menopausal Symptoms: A Systematic Review and Meta-analysis","volume":"315","author":"Franco","year":"2016","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1089\/acm.2017.0118","article-title":"Effects of Phytoestrogens on Depressive Symptoms in Climacteric Women: A Meta-Analysis of Randomized Controlled Trials","volume":"24","author":"Su","year":"2018","journal-title":"J. Altern. Complement. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Landa, J.F., and Cueto-Escobedo, J. (2017). Use of Phytoestrogens for the Treatment of Psychiatric Symptoms Associated with Menopause Transition. A Multidisciplinary Look at Menopause, InTech Open.","DOI":"10.5772\/intechopen.70114"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/B978-0-444-64056-7.00005-2","article-title":"Chapter 5-Phytoestrogens as Potential Therapeutic Agents for the Treatment of Anxiety and Affective Disorders","volume":"Volume 58","year":"2018","journal-title":"Studies in Natural Products Chemistry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1207\/s15327914nc5501_1","article-title":"Estimated Asian adult soy protein and isoflavone intakes","volume":"55","author":"Messina","year":"2006","journal-title":"Nutr. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00280-019-03886-3","article-title":"Genistein combined with FOLFOX or FOLFOX\u2013Bevacizumab for the treatment of metastatic colorectal cancer: Phase I\/II pilot study","volume":"84","author":"Pintova","year":"2019","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s12020-007-9006-1","article-title":"Genistein affects HER2 protein concentration, activation, and promoter regulation in BT-474 human breast cancer cells","volume":"32","author":"Sakla","year":"2007","journal-title":"Endocrine"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Johnson, A., Roberts, L., and Elkins, G. (2019). Complementary and Alternative Medicine for Menopause. J. Evid. Based Integr. Med., 24.","DOI":"10.1177\/2515690X19829380"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12935-018-0559-2","article-title":"Estrogen receptor modulators genistein, daidzein and ERB-041 inhibit cell migration, invasion, proliferation and sphere formation via modulation of FAK and PI3K\/AKT signaling in ovarian cancer","volume":"18","author":"Chan","year":"2018","journal-title":"Cancer Cell Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.foodres.2017.10.054","article-title":"Soybean soluble polysaccharide enhances absorption of soybean genistein in mice","volume":"103","author":"Lu","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.exppara.2018.01.013","article-title":"Impact of treatment with a Protein Tyrosine Kinase Inhibitor (Genistein) on acute and chronic experimental Schistosoma mansoni infection","volume":"185","author":"Sobhy","year":"2018","journal-title":"Exp. Parasitol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1617202","DOI":"10.1155\/2018\/1617202","article-title":"Modulation of Adipocyte Differentiation and Proadipogenic Gene Expression by Sulforaphane, Genistein, and Docosahexaenoic Acid as a First Step to Counteract Obesity","volume":"2018","author":"Valli","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.3389\/fphys.2018.01493","article-title":"Dietary Genistein Alleviates Lipid Metabolism Disorder and Inflammatory Response in Laying Hens With Fatty Liver Syndrome","volume":"9","author":"Lv","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.phymed.2018.03.039","article-title":"G protein-coupled estrogen receptor is involved in the anti-inflammatory effects of genistein in microglia","volume":"43","author":"Du","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1677\/joe.0.1470295","article-title":"Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids","volume":"147","author":"Evans","year":"1995","journal-title":"J. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15511","DOI":"10.1016\/S0021-9258(19)49564-1","article-title":"Genistein inhibits protein histidine kinase","volume":"267","author":"Huang","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.2174\/092986707782023325","article-title":"Phytochemical genistein in the regulation of vascular function: New insights","volume":"14","author":"Si","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"839","DOI":"10.7326\/0003-4819-146-12-200706190-00005","article-title":"Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: A randomized trial","volume":"146","author":"Marini","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1006\/taap.2000.9019","article-title":"Dietary genistein inactivates rat thyroid peroxidase in vivo without an apparent hypothyroid effect","volume":"168","author":"Chang","year":"2000","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1081\/RRS-120014613","article-title":"The influence of coumestrol, zearalenone, and genistein administration on insulin receptors and insulin secretion in ovariectomized rats","volume":"22","author":"Nogowski","year":"2002","journal-title":"J. Recept. Signal. Transduct. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0960-0760(02)00021-3","article-title":"Effects of flavonoid phytochemicals on cortisol production and on activities of steroidogenic enzymes in human adrenocortical H295R cells","volume":"80","author":"Ohno","year":"2002","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.lfs.2003.04.006","article-title":"Genistein administration decreases serum corticosterone and testosterone levels in rats","volume":"74","author":"Ohno","year":"2003","journal-title":"Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ctcp.2019.07.007","article-title":"Complementary and alternative medicine for natural and treatment-induced vasomotor symptoms: An overview of systematic reviews and meta-analyses","volume":"36","author":"Guo","year":"2019","journal-title":"Complement. Ther. Clin. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.maturitas.2019.03.023","article-title":"Effect of oral phytoestrogens on endometrial thickness and breast density of perimenopausal and postmenopausal women: A systematic review and meta-analysis","volume":"124","author":"Mareti","year":"2019","journal-title":"Maturitas"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.6026\/97320630015011","article-title":"Molecular docking analysis of nuclear factor-\u03baB and genistein interaction in the context of breast cancer","volume":"15","author":"Mukund","year":"2019","journal-title":"Bioinformation"},{"key":"ref_31","first-page":"1","article-title":"The phytoestrogen genistein affects inflammatory-related genes expression depending on the ER\u03b1\/ER\u03b2 ratio in breast cancer cells","volume":"2","author":"Pons","year":"2019","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jcjd.2019.04.007","article-title":"Effectiveness of genistein supplementation on metabolic factors and antioxidant status in postmenopausal women with type-2 diabetes mellitus","volume":"43","author":"Braxas","year":"2019","journal-title":"Can. J. Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.nutres.2019.06.007","article-title":"Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study","volume":"68","author":"Nayeem","year":"2019","journal-title":"Nutr. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1271\/bbb.100238","article-title":"Genistein regulated serotonergic activity in the hippocampus of ovariectomized rats under forced swimming stress","volume":"74","author":"Kageyama","year":"2010","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/978-3-319-78009-2_15","article-title":"Menopause and Ageing","volume":"1","author":"Schenker","year":"2018","journal-title":"Reproductive Medicine for Clinical Practice. Reproductive Medicine for Clinicians"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.maturitas.2016.02.003","article-title":"Menopausal vasomotor symptoms are associated with poor self-assessed work ability","volume":"87","author":"Gartoulla","year":"2016","journal-title":"Maturitas"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.fertnstert.2015.09.017","article-title":"Vasomotor and sexual symptoms in older Australian women: A cross-sectional study","volume":"105","author":"Zeleke","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1093\/aje\/153.8.790","article-title":"Soy product intake and hot flashes in Japanese women: Results from a community-based prospective study","volume":"153","author":"Nagata","year":"2001","journal-title":"Am. J. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/01.GME.0000109314.11228.E5","article-title":"Effects of genistein on hot flushes in early postmenopausal women: A randomized, double-blind EPT-and placebo-controlled study","volume":"11","author":"Crisafulli","year":"2004","journal-title":"Menopause"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"13115","DOI":"10.1002\/jcb.28584","article-title":"Estrogen receptor genes polymorphisms determine serum lipid profile in healthy postmenopausal women treated with calcium, vitamin D, and genistein","volume":"120","author":"Linares","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1111\/j.1440-1681.2007.04658.x","article-title":"Sex hormones and the cardiovascular system: Effects on arterial function in women","volume":"34","author":"Teede","year":"2007","journal-title":"Clin. Exp. Pharmacol Physiol"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1210\/jc.2006-2295","article-title":"Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: A two-year randomized, double-blind, placebo-controlled study","volume":"92","author":"Atteritano","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1111\/eci.12139","article-title":"Genistein and endothelial function in postmenopausal women with metabolic syndrome","volume":"43","author":"Irace","year":"2013","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/00042192-200512020-00013","article-title":"Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women","volume":"12","author":"Crisafulli","year":"2005","journal-title":"Menopause"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1038\/sj.bjp.0702973","article-title":"Cardioprotection by the phytoestrogen genistein in experimental myocardial ischaemia-reperfusion injury","volume":"128","author":"Deodato","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jsbmb.2007.01.005","article-title":"Genistein--a dietary compound inducing hormonal and metabolic changes","volume":"105","author":"Szkudelska","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.2337\/diacare.25.10.1709","article-title":"Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes","volume":"25","author":"Jayagopal","year":"2002","journal-title":"Diabetes Care"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1210\/jc.2009-2779","article-title":"Genistein aglycone does not affect thyroid function: Results from a three-year, randomized, double-blind, placebo-controlled trial","volume":"95","author":"Bitto","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3366","DOI":"10.1210\/jc.2013-1180","article-title":"Genistein in the metabolic syndrome: Results of a randomized clinical trial","volume":"98","author":"Squadrito","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"De Gregorio, C., Marini, H., Alibrandi, A., Di Benedetto, A., Bitto, A., Adamo, E.B., Altavilla, D., Irace, C., Di Vieste, G., and Pancaldo, D. (2017). Genistein Supplementation and Cardiac Function in Postmenopausal Women with Metabolic Syndrome: Results from a Pilot Strain-Echo Study. Nutrients, 9.","DOI":"10.3390\/nu9060584"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1210\/jc.2008-0735","article-title":"The differential effect of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women: Relationship with the metabolic status","volume":"94","author":"Villa","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.clnu.2004.04.010","article-title":"Adiponectin, the missing link in insulin resistance and obesity","volume":"23","author":"Canete","year":"2004","journal-title":"Clin. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/dmrr.1201","article-title":"Visfatin in overweight\/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: A meta-analysis and systemic review","volume":"27","author":"Chang","year":"2011","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.bbr.2018.12.017","article-title":"Long-term ovariectomy increases anxiety- and despair-like behaviors associated with lower Fos immunoreactivity in the lateral septal nucleus in rats","volume":"360","author":"Caba","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1089\/jmf.2009.0271","article-title":"Genistein induces estrogen-like effects in ovariectomized rats but fails to increase cardiac GLUT4 and oxidative stress","volume":"13","author":"Markus","year":"2010","journal-title":"J. Med. Food"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.lfs.2006.03.022","article-title":"Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL\/KsJ-db\/db mice","volume":"79","author":"Choi","year":"2006","journal-title":"Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/dmrr.780","article-title":"Genistein and daidzein prevent diabetes onset by elevating insulin level and altering hepatic gluconeogenic and lipogenic enzyme activities in non-obese diabetic (NOD) mice","volume":"24","author":"Choi","year":"2008","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S0014-5793(01)02631-X","article-title":"Genistein, a soy isoflavone, is a potent alpha-glucosidase inhibitor","volume":"501","author":"Lee","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_59","first-page":"1361","article-title":"Insulin regulation of malic enzyme gene expression in rat liver: Evidence for nuclear proteins that bind to two putative insulin response elements","volume":"8","author":"Benito","year":"1994","journal-title":"Mol. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/BF01075922","article-title":"In vivo effects of vanadate on hepatic glycogen metabolizing and lipogenic enzymes in insulin-dependent and insulin-resistant diabetic animals","volume":"153","author":"Khandelwal","year":"1995","journal-title":"Mol. Cell Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40659-017-0140-9","article-title":"Awareness and current knowledge of breast cancer","volume":"50","author":"Akram","year":"2017","journal-title":"Biol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Collaborative Group on Hormonal Factors in Breast Cancer (2019). Type and timing of menopausal hormone therapy and breast cancer risk: Individual participant meta-analysis of the worldwide epidemiological evidence. Lancet, 394, 1159\u20131168.","DOI":"10.1016\/S0140-6736(19)31709-X"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.3945\/ajcn.2008.27029","article-title":"Soy consumption and prostate cancer risk in men: A revisit of a meta-analysis","volume":"89","author":"Yan","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1080\/01635580902825639","article-title":"Soy food consumption and risk of prostate cancer: A meta-analysis of observational studies","volume":"61","author":"Hwang","year":"2009","journal-title":"Nutr. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Chen, M., Rao, Y., Zheng, Y., Wei, S., Li, Y., Guo, T., and Yin, P. (2014). Association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women: A meta-analysis of epidemiological studies. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089288"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.canlet.2003.08.023","article-title":"Cytostatic and cytotoxic activity of synthetic genistein glycosides against human cancer cell lines","volume":"203","author":"Polkowski","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.canlet.2005.01.014","article-title":"In vitro toxicity evaluation in the development of new anticancer drugs-genistein glycosides","volume":"229","author":"Popiolkiewicz","year":"2005","journal-title":"Cancer Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6512","DOI":"10.3748\/wjg.v11.i41.6512","article-title":"Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis","volume":"11","author":"Gu","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_70","first-page":"3833","article-title":"Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo","volume":"58","author":"Hsieh","year":"1998","journal-title":"Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0925-4439(03)00082-6","article-title":"Inhibitory actions of genistein in human breast cancer (MCF-7) cells","volume":"1638","author":"Chen","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/35060032","article-title":"Cytoplasmic localization of p21Cip1\/WAF1 by Akt-induced phosphorylation in HER-2\/neu-overexpressing cells","volume":"3","author":"Zhou","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_73","first-page":"149","article-title":"Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent","volume":"113\u2013114","author":"Satoh","year":"2003","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/ncb1101-973","article-title":"HER-2\/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation","volume":"3","author":"Zhou","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.tiv.2007.01.023","article-title":"Preliminary studies on induction of apoptosis by genistein on HepG2 cell line","volume":"21","author":"Chodon","year":"2007","journal-title":"Toxicol. In Vitro"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/bjc.2017.323","article-title":"Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death","volume":"117","author":"Li","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1002\/ptr.3498","article-title":"Isoflavones as apoptosis inducers in human hepatoma HuH-7 cells","volume":"25","author":"Mansoor","year":"2011","journal-title":"Phytother. Res."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Wang, S.D., Chen, B.C., Kao, S.T., Liu, C.J., and Yeh, C.C. (2014). Genistein inhibits tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-26"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.bcp.2006.11.027","article-title":"Genistein induces apoptosis in human hepatocellular carcinomas via interaction of endoplasmic reticulum stress and mitochondrial insult","volume":"73","author":"Yeh","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Lee, S.R., Kwon, S.W., Lee, Y.H., Kaya, P., Kim, J.M., Ahn, C., Jung, E.M., Lee, G.S., An, B.S., and Jeung, E.B. (2019). Dietary intake of genistein suppresses hepatocellular carcinoma through AMPK-mediated apoptosis and anti-inflammation. BMC Cancer, 19.","DOI":"10.1186\/s12885-018-5222-8"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1007\/s13277-013-1542-0","article-title":"Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small-cell lung cancer cells","volume":"35","author":"Tian","year":"2014","journal-title":"Tumour. Biol."},{"key":"ref_82","first-page":"4","article-title":"Genistein induces apoptosis through upregulation of p53 signaling pathway","volume":"9","author":"Hong","year":"2008","journal-title":"J. Trop. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1053\/j.gastro.2008.02.090","article-title":"Diagnosis and treatment of hepatocellular carcinoma","volume":"134","author":"Marrero","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.3892\/ol.2016.4817","article-title":"Genistein inhibits A549 human lung cancer cell proliferation via miR-27a and MET signaling","volume":"12","author":"Yang","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1021\/bi901760d","article-title":"Genistein arrests cell cycle progression of A549 cells at the G(2)\/M phase and depolymerizes interphase microtubules through binding to a unique site of tubulin","volume":"49","author":"Mukherjee","year":"2010","journal-title":"Biochemistry"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00394-009-0044-8","article-title":"Genistein and beta-carotene enhance the growth-inhibitory effect of trichostatin A in A549 cells","volume":"49","author":"Shiau","year":"2010","journal-title":"Eur. J. Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1177\/147323001103900610","article-title":"Involvement of nuclear factor kappaB (NF-kappaB) in the downregulation of cyclooxygenase-2 (COX-2) by genistein in gastric cancer cells","volume":"39","author":"Li","year":"2011","journal-title":"J. Int. Med. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1080\/01635581.2013.810290","article-title":"Genistein induces G2\/M arrest in gastric cancer cells by increasing the tumor suppressor PTEN expression","volume":"65","author":"Liu","year":"2013","journal-title":"Nutr. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1158\/1055-9965.EPI-09-0856","article-title":"Soy consumption and colorectal cancer risk in humans: A meta-analysis","volume":"19","author":"Yan","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.canlet.2008.03.052","article-title":"Multi-targeted therapy of cancer by genistein","volume":"269","author":"Banerjee","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3748\/wjg.v11.i1.69","article-title":"Blocking effects of genistein on cell proliferation and possible mechanism in human gastric carcinoma","volume":"11","author":"Cui","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1258\/ebm.2011.010347","article-title":"Genistein attenuates WNT signaling by up-regulating sFRP2 in a human colon cancer cell line","volume":"236","author":"Zhang","year":"2011","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Wang, H., Li, Q., and Chen, H. (2012). Genistein affects histone modifications on Dickkopf-related protein 1 (DKK1) gene in SW480 human colon cancer cell line. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040955"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1006\/bbrc.2000.2444","article-title":"Estrogen receptor beta mRNA in colon cancer cells: Growth effects of estrogen and genistein","volume":"270","author":"Arai","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1207\/S15327914NC421_18","article-title":"Effects of soybean extract on morphology and survival of Caco-2, SW620, and HT-29 cells","volume":"42","author":"Zhu","year":"2002","journal-title":"Nutr. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.canlet.2004.06.010","article-title":"Inhibition of proliferation and induction of apoptosis by genistein in colon cancer HT-29 cells","volume":"215","author":"Yu","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Qi, W., Weber, C.R., Wasland, K., and Savkovic, S.D. (2011). Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-219"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.18632\/oncotarget.3064","article-title":"Genistein suppresses FLT4 and inhibits human colorectal cancer metastasis","volume":"6","author":"Xiao","year":"2015","journal-title":"Oncotarget"},{"key":"ref_99","first-page":"4101","article-title":"Protein tyrosine kinase and estrogen receptor-dependent pathways regulate the synthesis and distribution of glycosaminoglycans\/proteoglycans produced by two human colon cancer cell lines","volume":"27","author":"Chatzinikolaou","year":"2007","journal-title":"Anticancer Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1002\/pmic.200900662","article-title":"Global phosphoproteomic effects of natural tyrosine kinase inhibitor, genistein, on signaling pathways","volume":"10","author":"Yan","year":"2010","journal-title":"Proteomics"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4603","DOI":"10.18632\/oncotarget.2209","article-title":"Deregulation of the EGFR\/PI3K\/PTEN\/Akt\/mTORC1 pathway in breast cancer: Possibilities for therapeutic intervention","volume":"5","author":"Davis","year":"2014","journal-title":"Oncotarget"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1038\/sj.onc.1206583","article-title":"Inactivation of NF-kappaB by genistein is mediated via Akt signaling pathway in breast cancer cells","volume":"22","author":"Gong","year":"2003","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"6934","DOI":"10.1158\/0008-5472.CAN-04-4604","article-title":"Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells","volume":"65","author":"Li","year":"2005","journal-title":"Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1079\/BJN20051640","article-title":"Soya phytonutrients act on a panel of genes implicated with BRCA1 and BRCA2 oncosuppressors in human breast cell lines","volume":"95","author":"Caetano","year":"2006","journal-title":"Br. J. Nutr."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10549-006-9191-2","article-title":"Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha","volume":"99","author":"Seo","year":"2006","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4787","DOI":"10.1210\/jc.2008-1087","article-title":"Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: A follow-up study","volume":"93","author":"Marini","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ejphar.2008.04.049","article-title":"Effects of phytoestrogen genistein on cytogenetic biomarkers in postmenopausal women: 1 year randomized, placebo-controlled study","volume":"589","author":"Atteritano","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/mc.22100","article-title":"Genistein inhibits hepatocellular carcinoma cell migration by reversing the epithelial-mesenchymal transition: Partial mediation by the transcription factor NFAT1","volume":"54","author":"Dai","year":"2015","journal-title":"Mol. Carcinog."},{"key":"ref_109","first-page":"9073816","article-title":"The Phytoestrogen Genistein Produces Similar Effects as 17beta-Estradiol on Anxiety-Like Behavior in Rats at 12 Weeks after Ovariectomy","volume":"2017","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1159\/000317285","article-title":"Norepinephrine and serotonin transporter genes: Impact on treatment response in depression","volume":"62","author":"Baffa","year":"2010","journal-title":"Neuropsychobiology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"919","DOI":"10.30773\/pi.2018.06.29","article-title":"Genistein Improves the Major Depression through Suppressing the Expression of miR-221\/222 by Targeting Connexin 43","volume":"15","author":"Shen","year":"2018","journal-title":"Psychiatry Investig."},{"key":"ref_112","first-page":"164943","article-title":"Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study","volume":"2015","author":"Gupta","year":"2015","journal-title":"Adv. Pharmacol. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.maturitas.2010.11.012","article-title":"The effect of synthetic genistein on menopause symptom management in healthy postmenopausal women: A multi-center, randomized, placebo-controlled study","volume":"68","author":"Evans","year":"2011","journal-title":"Maturitas"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.physbeh.2014.05.020","article-title":"Perinatal exposure to genistein affects the normal development of anxiety and aggressive behaviors and nitric oxide system in CD1 male mice","volume":"133","author":"Filice","year":"2014","journal-title":"Physiol. Behav."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.pnpbp.2008.12.024","article-title":"Anxiolytic-like effect of phytoestrogen genistein in rats with long-term absence of ovarian hormones in the black and white model","volume":"33","author":"Saavedra","year":"2009","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"439","DOI":"10.4236\/pp.2012.34059","article-title":"Involvement of Estrogen Receptors in the Anxiolytic-Like Effect of Phytoestrogen Genistein in Rats with 12-Weeks Postovariectomy","volume":"3","author":"Saavedra","year":"2012","journal-title":"Pharmacol. Pharm."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.psychres.2017.05.051","article-title":"Genistein alleviates anxiety-like behaviors in post-traumatic stress disorder model through enhancing serotonergic transmission in the amygdala","volume":"255","author":"Wu","year":"2017","journal-title":"Psychiatry Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.neuint.2013.12.002","article-title":"Lose dose genistein inhibits glucocorticoid receptor and ischemic brain injury in female rats","volume":"65","author":"Shi","year":"2014","journal-title":"Neurochem. Int."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s12031-007-0010-y","article-title":"Effects of genistein on hippocampal neurodegeneration of ovariectomized rats","volume":"31","author":"Xu","year":"2007","journal-title":"J. Mol. Neurosci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1017\/S0007114510002291","article-title":"Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress","volume":"104","author":"Huang","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"192","DOI":"10.2174\/1389450118666170816123740","article-title":"The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism","volume":"20","author":"Hairi","year":"2019","journal-title":"Curr. Drug Targets"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1080\/09513590701585037","article-title":"Differential effects of various progestogens on metabolic risk factors for breast cancer","volume":"23","author":"Campagnoli","year":"2007","journal-title":"Gynecol. Endocrinol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Wachtel, M.S., Yang, S., Dissanaike, S., and Margenthaler, J.A. (2015). Hormone Replacement Therapy, Likely Neither Angel Nor Demon. PloS ONE, 10.","DOI":"10.1371\/journal.pone.0138556"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/SPV.0000000000000559","article-title":"A Review of Phytoestrogens and Their Association With Pelvic Floor Conditions","volume":"24","author":"Meyer","year":"2018","journal-title":"Female Pelvic Med. Reconstr. Surg."},{"key":"ref_125","first-page":"741","article-title":"Analysis on the mechanism of Helicobacter pylori-induced apoptosis in gastric cancer cell line BGC-823","volume":"16","author":"Chen","year":"2005","journal-title":"Int. J. Mol. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ijc.31095","article-title":"Dietary intake of isoflavones and coumestrol and the risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial","volume":"142","author":"Reger","year":"2018","journal-title":"Int. J. Cancer"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/21\/3892\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:30:13Z","timestamp":1760189413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/21\/3892"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,29]]},"references-count":126,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["molecules24213892"],"URL":"https:\/\/doi.org\/10.3390\/molecules24213892","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,29]]}}}