Effect of bisphenol-A on the expression of selected genes involved in cell cycle and apoptosis in the OVCAR-3 cell line

Oestrogens, Xenoestrogens and Hormone-Dependent Cancers

“…Basal and mitogen-induced cell growth is regulated by cell cycle inhibitors, which can bind to and inhibit the Cdks (such as p15, p16, p21, p27, p57). The results of our study [40] demonstrated that BPA promotes G1 to S-phase progression by stimulating the expression of cyclin D1, CDK4, E2F1, E2F3 and PCNA while inhibiting the expression of inhibitors (p21WAF1/CIP1, Weel-1 and GADD45 alpha) and progression from G2 into mitosis by stimulating the expression of cyclin A in ovarian cancer cells OVCAR-3, Figure 20. The results of our study [40] additionally demonstrated that the suppression of p21/WAF mRNA, a marker of poor overall survival in ovarian cancer patients, was under the influence of BPA.…”

“…In our previously published study, we demonstrated that inhibition of the caspase-3 activity had no effect on DNA fragmentation in cells exposed to BPA [40]. We demonstrated that BPA acts by suppressing the expression of pro-apoptotic genes, such as FAS, FADD, RAIDD, caspase-8, -10, -3, -6, -7, CAD, Bax, Bak, Bok and Apaf-1, and inducing the expression of pro-survival genes, such as Bcl-x and Mcl-1.…”

“…BPA can increase cell proliferation in a dose-dependent manner in OVCAR-3 human ovarian cancer cells [40], MCF-7 breast cancer cells [41] and HeLa cells [42], Figure 19. [40] Alterations in the mechanisms controlling cell cycle progression play a relevant role in the pathogenesis of different types of human neoplasia.…”

“…[40] Alterations in the mechanisms controlling cell cycle progression play a relevant role in the pathogenesis of different types of human neoplasia. As the cell cycle is regulated by the coordinate action of cyclin-dependent kinases (cdk), specific cyclin proteins and cdk inhibitors, we focused on cell cycle associated gene analysis.…”

Cell growth of BG-1 ovarian cancer cells is promoted by di-n-butyl phthalate and hexabromocyclododecane via upregulation of the cyclin D and cyclin-dependent kinase-4 genes

“…In cell cycling pathways, cyclin D and cdk-4 form a complex and promote cell cycle progression through the G1 phase. p21, the cdk inhibitor, disrupts the formation of the cyclin-cdk complex and inhibits G1/S transition (34,35). E2 is reported to stimulate cellular proliferation, PR expression and morphological differentiation in the endometrial Ishikawa cancer cell line by stimulating the transition of cell cycle via upregulation of cyclin D and cyclin A and downregulation of p21, p27 and p53 (36,37).…”