Bisphenol A at Low Nanomolar Doses Confers Chemoresistance in Estrogen Receptor-α–Positive and –Negative Breast Cancer Cells

Abstract

BackgroundResistance to chemotherapy is a major problem facing breast cancer patients, and identifying potential contributors to chemoresistance is a critical area of research. Bisphenol A (BPA) has long been suspected to promote carcinogenesis, but the high doses of BPA used in many studies generated conflicting results. In addition, the mechanism by which BPA exerts its biological actions is unclear. Although estrogen has been shown to antagonize anticancer drugs, the role of BPA in chemoresistance has not been examined.ObjectiveThe objective of our study was to determine whether BPA at low nanomolar concentrations opposes the action of doxorubicin, cisplatin, and vinblastine in the estrogen receptor-α (ERα)-positive T47D and the ERα-negative MDA-MB-468 breast cancer cells.MethodsWe determined the responsiveness of cells to anticancer drugs and BPA using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity assay. Specific ERα and ERβ inhibitors and real-time polymerase chain reaction were used to identify potential receptor(s) that mediate the actions of BPA. Expression of antiapoptotic proteins was assessed by Western blotting.ResultsBPA antagonizes the cytotoxicity of multiple chemotherapeutic agents in both ERα-positive and -negative breast cancer cells independent of the classical ERs. Both cell types express alternative ERs, including G-protein–coupled receptor 30 (GPR30) and members of the estrogen-related receptor family. Increased expression of antiapoptotic proteins is a potential mechanism by which BPA exerts its anticytotoxic effects.ConclusionsBPA at environmentally relevant doses reduces the efficacy of chemotherapeutic agents. These data provide considerable support to the accumulating evidence that BPA is hazardous to human health.

Effect of bisphenol A on human endometrial stromal fibroblasts in vitro

“…BPA selectively binds to oestrogen receptors a and b and has a higher affinity for oestrogen receptor b in select target cells (Han et al, 2002;Lapensee et al, 2009). BPA may also affect oestrogen receptor b-mediated transcription of target genes by differential degradation of nuclear receptors (Masuyama and Hiramatsu, 2004).…”

Impact of Environmental Contaminants on Breast Cancer / Wpływ Zanieczyszczenia Środowiska Na Raka Piersi

“…BPA was also found to antagonize the cytotoxicity of multiple chemotherapeutic agents in both ER-α-positive and -negative breast cancer cells and consequently, at environmentally relevant doses, it reduced the efficacy of chemotherapeutic agents [140].…”

Endocrine Disruptors and Breast Cancer Risk - Time to Consider the Environment

“…Finally, BPA can antagonize the cytotoxicity of chemotherapeutic agents doxorubicin, cisplatin, and vinblastine in vitro independent of classical estrogen receptors, thus it may affect the outcomes of chemotherapy (LaPensee et al, 2009;.…”