The effects of single walled carbon nanotubes (SWCNTs) on proliferation and apoptosis of human peripheral blood mononuclear cells (PBMCs)

Abstract

Breast cancer is one of the leading causes of cancer-related morbidity and mortality among women worldwide. Phytoestrogens, plant-derived polyphenols that structurally and functionally mimic 17β-estradiol, the mammalian estrogen hormone, are known to modulate multiple molecular targets in breast cancer cells. The structural and chemical similarities to estradiol enable phytoestrogens to exert estrogenic or antiestrogenic activities by binding to the estrogen receptors. Although phytoestrogens have low affinity for estrogen receptors, they are able to compete with 17β-estradiol for the ligand-binding domain of the receptors. Phytoestrogens trigger epigenomic effects that could be beneficial in breast cancer prevention and/or treatment. Few studies have focused on the cytotoxic and structure-activity relationships of phytoestrogen analogs and derivatives with more effective anticancer properties than their corresponding parent compounds. Phytoestrogens and their analogs and derivatives bind to estrogen receptors, with a preferential affinity for ERβ, and inhibit the growth promoting activity of ERα. These bioactive compounds also exert growth inhibitory effects through various cell signaling pathways. At the level of cell cycle, they inhibit the expression of oncogenic cyclin D1, increase the expression of cyclin-dependent kinase inhibitors (p21, p27, and p57) and tumor suppressor genes (APC, ATM, PTEN, SERPINB5). Phytoestrogens and their analogs and derivatives mediate their effects on breast cancer by inhibiting estrogen synthesis and metabolism, as well as exerting antiangiogenic, antimetastatic, and epigenetic effects. Furthermore, these bioactive compounds reverse multi-drug resistance. This review offers a comprehensive summary of current literature and future perspectives on the in vitro molecular mechanisms of the anticancer activities of phytoestrogens and their analogs and derivatives on breast cancer.