Genistein, a soy phytoestrogen, prevents the growth of BG-1 ovarian cancer cells induced by 17β-estradiol or bisphenol A via the inhibition of cell cycle progression

Abstract

An endocrine disrupting chemical (EDC) is a global health concern. In this study, we examined the effects of genistein (GEN) on bisphenol A (BPA) or 17β-estradiol (E2)-induced cell growth and gene alterations of BG-1 ovarian cancer cells expressing estrogen receptors (ERs). In an in vitro cell viability assay, E2 or BPA significantly increased the growth of BG-1 cells. This increased proliferative activity was reversed by treatment with ICI 182,780, a well-known ER antagonist, while cell proliferation was further promoted in the presence of propyl pyrazole triol (PPT), an ERα agonist. These results imply that cell proliferation increased by E2 or BPA was mediated by ERs, particularly ERα. BPA clearly acted as a xenoestrogen in BG-1 ovarian cancer cells by mimicking E2 action. In contrast, GEN effectively suppressed BG-1 cell proliferation promoted by E2 or BPA by inhibiting cell cycle progression. E2 and BPA increased the expression of cyclin D1, a factor responsible for the G1/S cell cycle transition. They also decreased the expression of p21, a potent cyclin-dependent kinase (CDK) inhibitor that arrests the cell cycle in G1 phase, and promoted the proliferation of BG-1 cells. As shown by its repressive effect on cell growth, GEN decreased the expression of cyclin D1 augmented by E2 or BPA. On the other hand, GEN increased the p21 expression downregulated by E2 or BPA. Collectively, our findings suggest that GEN, a dietary phytoestrogen, has an inhibitory effect on the growth of estrogen-dependent cancers promoted by E2 or BPA.

Genistein Alleviates β-Amyloid-Induced Inflammatory Damage Through Regulating Toll-Like Receptor 4/Nuclear Factor κB

“…8,9 Genistein (GEN) is a major bioactive isoflavone obtained primarily from soybeans. 10 It has been demonstrated that GEN has numerous activities, such as inhibition of protein tyrosine kinase, antioxidation, antiapoptosis, and deregulation of mitochondrial membrane pore permeability.…”

Signaling Proteins and Pathways Affected by Flavonoids in Leukemia Cells

“…In our study, genistein and scutellarin EFFECT OF FLAVONOIDS ON SIGNALING PROTEINS 247 downregulate the expression of cyclin D1, which is a cell cycle regulatory protein and the regulation of cyclin D1 is responsible for the G1/S cell cycle transition (35,36). In a different study, baicalein exhibited induced cell cycle arrest in osteosarcoma cells by suppressing the expression levels of cyclin D1 and Cdk4 (35)(36)(37). Another plant-derived flavonoid, quercetin, was also shown to dysregulate the expression of cyclin D1 in cervical cancer, HeLa cells (35)(36)(37)(38).…”

“…Genistein induces a G2/M cell cycle arrest in PC3 and LNCaP, prostate cancer cells; H460 and H322, nonsmall cell lung cancer cells as well as MDA-MB-231 and MCF-10CA1a, breast cancer cells (40). Moreover, Scutellaria baicalensis can greatly inhibit hepatocellular carcinoma cell growth via the G 2 /M phase arrest (15,(35)(36)(37)(38)41). Genistein induced an upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells (42).…”

“…In a different study, baicalein exhibited induced cell cycle arrest in osteosarcoma cells by suppressing the expression levels of cyclin D1 and Cdk4 (35)(36)(37). Another plant-derived flavonoid, quercetin, was also shown to dysregulate the expression of cyclin D1 in cervical cancer, HeLa cells (35)(36)(37)(38). Previous studies have shown flavonoids inhibit cell proliferation through cell cycle arrest.…”

Anticancer effect of genistein on BG-1 ovarian cancer growth induced by 17 β-estradiol or bisphenol A via the suppression of the crosstalk between estrogen receptor alpha and insulin-like growth factor-1 receptor signaling pathways

“…Some ERs, meanwhile, may mediate cytoplasmic signaling cascades via nongenomic pathways by interacting with receptor tyrosine kinases in a cell membrane. Epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) are typical receptor tyrosine kinases that provoke a mitogenic cytoplasmic signaling by activating extracellular signaling-regulated kinase (ERK) cascade (Improta-Brears et al, 1999) and phosphatidylinositol 3-kinase (PI3-kinase) route (Castoria et al, 2001;Sun et al, 2001) and they are also closely linked to ER signaling, thus providing an intricate pathogenesis in estrogen-dependent cancers (Massarweh and Schiff, 2006). Toxicology and Applied Pharmacology 272 (2013) [637][638][639][640][641][642][643][644][645][646] In the present study, we focused on the specific crosstalk between ER and IGF-1R signaling pathways in estrogen-responsive BG-1 ovarian cancer.…”