Bisphenol A prevents MCF‐7 breast cell apoptosis via the inhibition of progesterone receptor transactivation

Abstract

2,2-Bis(4-hydroxyphenyl)propane (bisphenol A; BPA) is an environmental endocrinedisrupting chemical. It mimics the effects of estrogen at multiple levels by activating estrogen receptors (ERs); however, BPA also affects the proliferation of human breast cancer cells independent of ERs. Although BPA inhibits progesterone (P4) signaling, the toxicological significance of its effects remain unknown. Tripartite motif-containing 22 (TRIM22) has been identified as a P4-responsive and apoptosis-related gene. Nevertheless, it has not yet been established whether exogenous chemicals change TRIM22 gene levels. Therefore, the present study investigated the effects of BPA on P4 signaling and TRIM22 and TP53 expression in human breast carcinoma MCF-7 cells. In MCF-7 cells incubated with various concentrations of P4, TRIM22 messenger RNA (mRNA) levels increased in a dose-dependent manner. P4 induced apoptosis and decreased viability in MCF-7 cells. The knockdown of TRIM22 abolished P4-induced decreases in cell viability and P4-induced apoptosis. P4 increased TP53 mRNA expression and p53knockdown decrease the basal level of TRIM22 and P4 increased TRIM22 mRNA expression independent of p53 expression. BPA attenuated P4-induced increases in the ratio of cell apoptosis in a concentration-dependent manner, and the P4-induced decreases in cell viability was abolished in the presence of 100 nM and higher BPA concentrations. Furthermore, BPA inhibited P4-induced TRIM22 and TP53 expression.In conclusion, BPA inhibited P4-induced apoptosis in MCF-7 cells via the inhibition of P4 receptor transactivation. TRIM22 gene has potential as a biomarker for investigating the disruption of P4 signaling by chemicals.

Decamethylcyclopentasiloxane affects estradiol production in female rats but not H295R cells

“…The mechanisms of action for EDCs are mainly divided into two types: through nuclear receptors or steroidogenesis-related enzymes (Diamanti-Kandarakis et al, 2009). Several assays detect EDCs that exert their effects through nuclear receptors both in vivo and in vitro (Clode, 2006;Martin-Yken, 2020;Ogawa et al, 2021Ogawa et al, , 2023Scholz et al, 2013), whereas an in vitro steroidogenesis assay using the human H295R adrenal carcinoma cell line was only developed in the OECD conceptual framework to test and assessment of EDCs (OECD, 2018(OECD, , 2022. The steroidogenesis assay using H295R cells that encode all the key enzymes for steroidogenesis is the in vitro test system used to investigate the effects of compounds on steroid hormone biosynthesis, specifically E2 and T in gonads although the cells are as a model for studies on adrenal steroidogenesis.…”