The authors acknowledge the use of OpenAI’s ChatGPT as an assistive tool for English language improvement and for conceptual support in preparing schematic figure layouts. All scientific content, interpretations, and final figures were critically reviewed, edited, and approved by the authors.
The authors gratefully acknowledge the support from the Amity Institute of Health Allied Sciences, Amity University, Uttar Pradesh, for encouraging the study and for providing infrastructural and administrative support. The authors are also thankful to the South African Technology Innovation Agency for providing time, resources, and infrastructure to do this publication.
Author contributions
ST: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. MGM: Validation, Writing—review & editing, Supervision. Both authors read and approved the submitted version.
Conflicts of interest
Both authors declare that they have no conflicts of interest.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA, et al. Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits.Oxid Med Cell Longev. 2021;2021:3268136. [DOI] [PubMed] [PMC]
Goh YX, Jalil J, Lam KW, Husain K, Premakumar CM. Genistein: A Review on its Anti-Inflammatory Properties.Front Pharmacol. 2022;13:820969. [DOI] [PubMed] [PMC]
Messina M. Soy and Health Update: Evaluation of the Clinical and Epidemiologic Literature.Nutrients. 2016;8:754. [DOI] [PubMed] [PMC]
Wu AH, Yu MC, Tseng C, Pike MC. Epidemiology of soy exposures and breast cancer risk.Br J Cancer. 2008;98:9–14. [DOI] [PubMed] [PMC]
Yan L, Spitznagel EL. Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis.Am J Clin Nutr. 2009;89:1155–63. [DOI] [PubMed]
Zhang K, Wang J, Xu B. Critical Review on Molecular Mechanisms for Genistein's Beneficial Effects on Health Through Oxidative Stress Reduction.Antioxidants (Basel). 2025;14:904. [DOI] [PubMed] [PMC]
Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes.Nutr Cancer. 2006;55:1–12. [DOI] [PubMed]
Hsiao YH, Ho CT, Pan MH. Bioavailability and health benefits of major isoflavone aglycones and their metabolites.J Funct Foods. 2020;74:104164. [DOI]
Rasheed S, Rehman K, Shahid M, Suhail S, Akash MSH. Therapeutic potentials of genistein: New insights and perspectives.J Food Biochem. 2022;46:e14228. [DOI] [PubMed]
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.PLoS Med. 2009;6:e1000100. [DOI] [PubMed] [PMC]
Yang Z, Kulkarni K, Zhu W, Hu M. Bioavailability and pharmacokinetics of genistein: mechanistic studies on its ADME.Anticancer Agents Med Chem. 2012;12:1264–80. [DOI] [PubMed] [PMC]
Kwon H, Han H, Oh Y, Kim Y, Kim J. Anti-cancer effects of genistein supplementation and moderate-intensity exercise in high-fat diet-induced breast cancer via regulation of inflammation and adipose tissue metabolism in vivo and in vitro.BMC Complement Med Ther. 2025;25:223. [DOI] [PubMed] [PMC]
Kciuk M, Kruczkowska W, Wanke K, Gałęziewska J, Kołat D, Mujwar S, et al. The Role of Genistein in Type 2 Diabetes and Beyond: Mechanisms and Therapeutic Potential.Molecules. 2025;30:1068. [DOI] [PubMed] [PMC]
Wu Z, Liu L. The protective activity of genistein against bone and cartilage diseases.Front Pharmacol. 2022;13:1016981. [DOI] [PubMed] [PMC]
Nazari-Khanamiri F, Ghasemnejad-Berenji M. Cellular and molecular mechanisms of genistein in prevention and treatment of diseases: An overview.J Food Biochem. 2021;45:e13972. [DOI] [PubMed]
Messina M. Insights gained from 20 years of soy research.J Nutr. 2010;140:2289S–95S. [DOI] [PubMed]
Hsieh CY, Santell RC, Haslam SZ, Helferich WG. Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo.Cancer Res. 1998;58:3833–8. [PubMed]
Sirtori CR, Lovati MR. Soy proteins and cardiovascular disease.Curr Atheroscler Rep. 2001;3:47–53. [DOI] [PubMed]
Hodis HN, Mack WJ, Kono N, Azen SP, Shoupe D, Hwang-Levine J, et al.; Women's Isoflavone Soy Health Research Group. Isoflavone soy protein supplementation and atherosclerosis progression in healthy postmenopausal women: a randomized controlled trial.Stroke. 2011;42:3168–75. [DOI] [PubMed] [PMC]
Setchell KD, Cassidy A. Dietary isoflavones: biological effects and relevance to human health.J Nutr. 1999;129:758S–67S. [DOI] [PubMed]
Arjmandi BH, Alekel L, Hollis BW, Amin D, Stacewicz-Sapuntzakis M, Guo P, et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis.J Nutr. 1996;126:161–7. [DOI] [PubMed]
Ma D, Qin L, Wang P, Katoh R. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials.Clin Nutr. 2008;27:57–64. [DOI] [PubMed]
Jayagopal V, Albertazzi P, Kilpatrick ES, Howarth EM, Jennings PE, Hepburn DA, et al. Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes.Diabetes Care. 2002;25:1709–14. [DOI] [PubMed]
Gilbert ER, Liu D. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function.Food Funct. 2013;4:200–12. [DOI] [PubMed] [PMC]
Mezei O, Banz WJ, Steger RW, Peluso MR, Winters TA, Shay N. Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells.J Nutr. 2003;133:1238–43. [DOI] [PubMed]
Kim H, Peterson TG, Barnes S. Mechanisms of action of the soy isoflavone genistein: emerging role for its effects via transforming growth factor beta signaling pathways.Am J Clin Nutr. 1998;68:1418S–25S. [DOI] [PubMed]
Li Y, Kong D, Wang Z, Sarkar FH. Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research.Pharm Res. 2010;27:1027–41. [DOI] [PubMed] [PMC]
Yu J, Bi X, Yu B, Chen D. Isoflavones: Anti-Inflammatory Benefit and Possible Caveats.Nutrients. 2016;8:361. [DOI] [PubMed] [PMC]
Bagheri M, Joghataei M, Mohseni S, Roghani M. Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer's disease.Neurobiol Learn Mem. 2011;95:270–6. [DOI] [PubMed]
Mas-Bargues C, Borrás C, Viña J. The multimodal action of genistein in Alzheimerʼs and other age-related diseases.Free Radic Biol Med. 2022;183:127–37. [DOI] [PubMed]
Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and antipromotional effects of the soybean isoflavone genistein.Proc Soc Exp Biol Med. 1995;208:124–30. [DOI] [PubMed]
Katanić Stanković JS, Mihailović N, Mihailović V. Genistein: Advances on Resources, Biosynthesis Pathway, Bioavailability, Bioactivity, and Pharmacology. In: Xiao J, editor. Handbook of Dietary Flavonoids. Cham: Springer International Publishing; 2023. pp. 1–40. [DOI]
Jaiswal N, Akhtar J, Singh SP, Badruddeen, Ahsan F. An Overview on Genistein and its Various Formulations.Drug Res (Stuttg). 2019;69:305–13. [DOI] [PubMed]
Meeran SM, Katiyar SK. Cell cycle control as a basis for cancer chemoprevention through dietary agents.Front Biosci. 2008;13:2191–202. [DOI] [PubMed] [PMC]
Sampey BP, Lewis TD, Barbier CS, Makowski L, Kaufman DG. Genistein effects on stromal cells determines epithelial proliferation in endometrial co-cultures.Exp Mol Pathol. 2011;90:257–63. [DOI] [PubMed] [PMC]
Naeem H, Momal U, Imran M, Shahbaz M, Hussain M, Alsagaby SA, et al. Anticancer perspectives of genistein: a comprehensive review.Int J Food Prop. 2023;26:3305–41. [DOI]
Chimento A, Luca AD, DʼAmico M, Amicis FD, Pezzi V. The Involvement of Natural Polyphenols in Molecular Mechanisms Inducing Apoptosis in Tumor Cells: A Promising Adjuvant in Cancer Therapy.Int J Mol Sci. 2023;24:1680. [DOI] [PubMed] [PMC]
Li Y, Zhang J, Chen R, Chen L, Chen S, Yang X, et al. Genistein mitigates oxidative stress and inflammation by regulating Nrf2/HO-1 and NF-κB signaling pathways in hypoxic-ischemic brain damage in neonatal mice.Ann Transl Med. 2022;10:32. [DOI] [PubMed] [PMC]
Russo M, Russo GL, Daglia M, Kasi PD, Ravi S, Nabavi SF, et al. Understanding genistein in cancer: The “good” and the “bad” effects: A review.Food Chem. 2016;196:589–600. [DOI] [PubMed]
Tuli HS, Tuorkey MJ, Thakral F, Sak K, Kumar M, Sharma AK, et al. Molecular Mechanisms of Action of Genistein in Cancer: Recent Advances.Front Pharmacol. 2019;10:1336. [DOI] [PubMed] [PMC]
Meeran SM, Patel SN, Li Y, Shukla S, Tollefsbol TO. Bioactive dietary supplements reactivate ER expression in ER-negative breast cancer cells by active chromatin modifications.PLoS One. 2012;7:e37748. [DOI] [PubMed] [PMC]
Majid S, Dar AA, Shahryari V, Hirata H, Ahmad A, Saini S, et al. Genistein reverses hypermethylation and induces active histone modifications in tumor suppressor gene B-Cell translocation gene 3 in prostate cancer.Cancer. 2010;116:66–76. [DOI] [PubMed] [PMC]
Xie Q, Bai Q, Zou L, Zhang Q, Zhou Y, Chang H, et al. Genistein inhibits DNA methylation and increases expression of tumor suppressor genes in human breast cancer cells.Genes Chromosomes Cancer. 2014;53:422–31. [DOI] [PubMed]
Fang MZ, Chen D, Sun Y, Jin Z, Christman JK, Yang CS. Reversal of hypermethylation and reactivation of p16INK4a, RARβ, and MGMT genes by genistein and other isoflavones from soy.Clin Cancer Res. 2005;11:7033–41. [DOI] [PubMed]
Doghish AS, Abdel Mageed SS, Mohammed OA, Abdel-Reheim MA, Zaki MB, Mohamed AH, et al. Natural compounds as regulators of miRNAs: exploring a new avenue for treating colorectal cancer.Funct Integr Genomics. 2025;25:42. [DOI] [PubMed]
Li Y, Chen H, Hardy TM, Tollefsbol TO. Epigenetic regulation of multiple tumor-related genes leads to suppression of breast tumorigenesis by dietary genistein.PLoS One. 2013;8:e54369. [DOI] [PubMed] [PMC]
Li Y, Vandenboom TG 2nd, Wang Z, Kong D, Ali S, Philip PA, et al. miR-146a suppresses invasion of pancreatic cancer cells.Cancer Res. 2010;70:1486–95. [DOI] [PubMed] [PMC]
Ruiz-Manriquez LM, Estrada-Meza C, Benavides-Aguilar JA, Ledesma-Pacheco SJ, Torres-Copado A, Serrano-Cano FI, et al. Phytochemicals mediated modulation of microRNAs and long non-coding RNAs in cancer prevention and therapy.Phytother Res. 2022;36:705–29. [DOI] [PubMed]
Hayakawa S, Ohishi T, Oishi Y, Isemura M, Miyoshi N. Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol.Antioxidants (Basel). 2022;11:2352. [DOI] [PubMed] [PMC]
Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases.J Biol Chem. 1987;262:5592–5. [PubMed]
Naponelli V, Piscazzi A, Mangieri D. Cellular and Molecular Mechanisms Modulated by Genistein in Cancer.Int J Mol Sci. 2025;26:1114. [DOI] [PubMed] [PMC]
Markovits J, Linassier C, Fossé P, Couprie J, Pierre J, Jacquemin-Sablon A, et al. Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II.Cancer Res. 1989;49:5111–7. [PubMed]
Sarkar FH, Li Y. Mechanisms of cancer chemoprevention by soy isoflavone genistein.Cancer Metastasis Rev. 2002;21:265–80. [DOI] [PubMed]
Li Y, Sarkar FH. Down-regulation of invasion and angiogenesis-related genes identified by cDNA microarray analysis of PC3 prostate cancer cells treated with genistein.Cancer Lett. 2002;186:157–64. [DOI] [PubMed]
Tanos V, Brzezinski A, Drize O, Strauss N, Peretz T. Synergistic inhibitory effects of genistein and tamoxifen on human dysplastic and malignant epithelial breast cells in vitro.Eur J Obstet Gynecol Reprod Biol. 2002;102:188–94. [DOI] [PubMed]
Cheng WX, Huang H, Chen JH, Zhang TT, Zhu GY, Zheng ZT, et al. Genistein inhibits angiogenesis developed during rheumatoid arthritis through the IL-6/JAK2/STAT3/VEGF signalling pathway.J Orthop Translat. 2019;22:92–100. [DOI] [PubMed] [PMC]
Clarke R, Liu MC, Bouker KB, Gu Z, Lee RY, Zhu Y, et al. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling.Oncogene. 2003;22:7316–39. [DOI] [PubMed]
Chen CY, Kao CL, Liu CM. The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway.Int J Mol Sci. 2018;19:2729. [DOI] [PubMed] [PMC]
Farruggio S, Cocomazzi G, Marotta P, Romito R, Surico D, Calamita G, et al. Genistein and 17β-Estradiol Protect Hepatocytes from Fatty Degeneration by Mechanisms Involving Mitochondria, Inflammasome and Kinases Activation.Cell Physiol Biochem. 2020;54:401–16. [DOI] [PubMed]
Han J, Kurita Y, Isoda H. Genistein-induced G2/M cell cycle arrest of human intestinal colon cancer Caco-2 cells is associated with Cyclin B1 and Chk2 down-regulation.Cytotechnology. 2013;65:973–8. [DOI] [PubMed] [PMC]
Pratheeshkumar P, Sreekala C, Zhang Z, Budhraja A, Ding S, Son Y, et al. Cancer prevention with promising natural products: mechanisms of action and molecular targets.Anticancer Agents Med Chem. 2012;12:1159–84. [DOI] [PubMed] [PMC]
Zhao Q, Li Y, Sun Q, Wang R, Lu H, Zhang X, et al. Self-assembled genistein nanoparticles suppress the epithelial-mesenchymal transition in glioblastoma by targeting MMP9.Mater Today Bio. 2025;31:101606. [DOI] [PubMed] [PMC]
Iqbal FM, Rodríguez-Nogales C, Boulens N, Delie F. Formulation and optimization of transferrin-modified genistein nanocrystals: In vitro anti-cancer assessment and pharmacokinetic evaluation.Int J Pharm. 2024;667:124863. [DOI] [PubMed]
Gao R, Lin P, Yang W, Fang Z, Gao C, Cheng B, et al. Bio-Inspired Nanodelivery Platform: Platelet Membrane-Cloaked Genistein Nanosystem for Targeted Lung Cancer Therapy.Int J Nanomedicine. 2024;19:10455–78. [DOI] [PubMed] [PMC]
Zhang H, Liu G, Zeng X, Wu Y, Yang C, Mei L, et al. Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells.Int J Nanomedicine. 2015;10:2461–73. [DOI] [PubMed] [PMC]
Skrajnowska D, Bielecki W, Szterk A, Ofiara K, Bobrowska-Korczak B. Genistein Supplementation and Bone Health in Breast Cancer in Rats.Nutrients. 2024;16:912. [DOI] [PubMed] [PMC]
Navarro-Marchal SA, Griñán-Lisón C, Entrena J, Ruiz-Alcalá G, Tristán-Manzano M, Martin F, et al. Anti-CD44-Conjugated Olive Oil Liquid Nanocapsules for Targeting Pancreatic Cancer Stem Cells.Biomacromolecules. 2021;22:1374–88. [DOI] [PubMed]
Motawea A, Maria SN, Maria DN, Jablonski MM, Ibrahim MM. Genistein transfersome-embedded topical delivery system for skin melanoma treatment: in vitro and ex vivo evaluations.Drug Deliv. 2024;31:2372277. [DOI] [PubMed] [PMC]
Abriata JP, Luiz MT, Viegas JSR, Fumagalli F, Maria Gilde Melo S, da Silva Emery F, et al. Poly-ε-caprolactone based nanoparticles for delivery of genistein in melanoma treatment.Braz J Pharm Sci. 2024;60:e22542. [DOI]
Goorbandi RG, Mohammadi MR, Malekzadeh K. Synthesizing efficacious genistein in conjugation with superparamagnetic Fe3O4 decorated with bio-compatible carboxymethylated chitosan against acute leukemia lymphoma.Biomater Res. 2020;24:9. [DOI] [PubMed] [PMC]
Xing Y, Shen W, Sun C, Wang R, Fan B, Liang G. Genistein-Chitosan Derivative Nanoparticles for Targeting and Enhancing the Anti-Breast Cancer Effect of Tamoxifen In Vitro.J Pharm Sci. 2024;113:2575–83. [DOI] [PubMed]
Terzioglu-Usak S, Yildiz MT, Goncu B, Ozten-Kandas N. Achieving the balance: Biphasic effects of genistein on PC-3 cells.J Food Biochem. 2019;43:e12951. [DOI] [PubMed]