Diethylhexyl Phthalate and Bisphenol A Promote Vincristine and Tamoxifen Resistance in Vitro.

ABSTRACT

Environmental estrogen active compounds are strong determinants of estrogen receptor (ER)-positive breast cancers, and increased evidence indicates their contribution to chemotherapy resistance. In the current study, the efficacy of vincristine and tamoxifen, with the presence of diethylhexyl phthalate (DEHP) and bisphenol A (BPA) and the possible involvement of estrogen and estrogen receptor-related mechanisms, was evaluated in an ER+ mammary tumor cancer cell line, MCF-7. Chemotherapeutics tamoxifen as an estrogen receptor modulator and vincristine as an antimitotic compound were selected for evaluation against the presence of common endocrine disrupters. BPA and DEHP preincubation at their proliferative concentrations for 4 h was found to decrease the cytotoxicity of vincristine. mRNA and protein expression of ESR1 and ESR 2 were decreased by vincristine, while this decrease was reversed by DEHP and BPA. Both BPA and DEHP were able to interfere with the cytotoxic activity of vincristine against MCF-7 cells through ESR1 and ESR2. This study provides in vitro toxicological evidence for vincristine resistance and its relation to estrogen active environmental pollutants in ER+ breast cancer cells.