Mechanism of action of genistein on breast cancer and differential effects of different age stages.

Context: Genistein, a soy-derived isoflavone, exhibits structural similarities with 17β-estradiol and demonstrates antioxidant, anti-inflammatory, and estrogenic properties. Despite its low bioavailability limiting its clinical application, it shows potential for breast cancer prevention and treatment.

Objective: This review aims to summarize the pharmacological effects and molecular mechanisms of genistein in breast cancer, focusing on its therapeutic potential, strategies to overcome bioavailability limitations, and its role in personalized medicine. Differential impacts among population subgroups are also discussed.

Methods: A systematic review was conducted using PubMed, ScienceDirect, and Google Scholar databases. Studies were selected based on their focus on genistein's mechanisms of action, strategies to enhance its bioavailability, and interactions with other therapies.

Results: Genistein exerted anticancer effects by modulating estrogen receptor β (ERβ), inhibiting angiogenesis, arresting the cell cycle, and inducing apoptosis. Its antioxidant properties help mitigate tumor-associated oxidative stress. Bioavailability enhancement strategies, such as nanoparticle and lipid-based formulations, show promise. Age-dependent effects were evident, with distinct responses observed in prepubertal, menopausal, and postmenopausal populations, underscoring its potential for personalized therapies. Furthermore, genistein influences epigenetic modifications, including DNA methylation and miRNA expression, bolstering its anticancer efficacy.

Conclusion: Genistein is a promising candidate for breast cancer therapy, particularly for personalized treatment. Strategies to enhance bioavailability and further clinical research are essential to optimize its therapeutic potential and evaluate its efficacy in combination therapies.