Journal
ENVIRONMENTAL HEALTH PERSPECTIVES
Volume 117, Issue 2, Pages 175-180Publisher
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.11788
Keywords
bisphenol A; breast cancer cells; chemotherapeutic agents; cytotoxicity; estrogen receptors
Funding
- National Institutes of Health (NIH) [ESO 12212, CA096613]
- Department of Defense [BC05725]
- Susan G. Komen Breast Cancer Foundation [BCRT87406]
- NIH [5T32ES007250]
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BACKGROUND: Resistance 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. OBJECTIVE: The 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-alpha (ER alpha)-positive T47D and the ER alpha-negative MDA-MB-468 breast cancer cells. METHODS: We 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 ER alpha and ER beta inhibitors and real-time polymerase chain reaction were used to identify potential receptor(s) that mediate the actions of BRA. Expression of antiapoptotic proteins was assessed by Western blotting. RESULTS: BPA antagonizes the cytotoxicity of multiple chemotherapeutic agents in both ER alpha-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. CONCLUSIONS: BPA 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.
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