Bisphenol A and estradiol are equipotent in antagonizing cisplatin-induced cytotoxicity in breast cancer cells.
Resistance to chemotherapy is a major problem facing breast cancer patients. Cisplatin, a highly effective DNA-damaging drug, has shown only little success in breast cancer treatment. We are reporting that low nanomolar doses of bisphenol A (BPA) or estradiol antagonize cisplatin cytotoxicity in breast cancer cells, with their effects not mediated via classical estrogen receptors. Although both compounds increase the expression of Bcl-2, a Bcl-2 inhibitor completely blocked the protective effects of BPA while only partially affecting those of estradiol. Blockade of BPA and E2 actions should sensitize ER-negative breast tumors to anti-cancer drugs and allow for the inclusion of cisplatin in treatment regimens.
Department of Cancer and Cell Biology, University of Cincinnati, OH 45267, USA.
Elizabeth W
EW
LaPensee
Christopher R
CR
LaPensee
Sejal
S
Fox
Sandy
S
Schwemberger
Scott
S
Afton
Nira
N
Ben-Jonathan
D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002469:Cell Separation; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098826:Bisphenol A Compounds
D000970:Antineoplastic Agents; D001559:Benzhydryl Compounds; D002945:Cisplatin; D004958:Estradiol; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds