. (2005) Effect of bisphenol A on drug efflux in BeWo, a human trophoblast-like cell line. Placenta, 26 Suppl.A, S96-S103. PMID: 15837075. Publisher's official version: http://dx.doi.org/10.1016/j.placenta.
Keywords:Bisphenol A (BPA), P-glycoprotein (P-gp), BeWo cells, Drug efflux and 17β-estradiol (E2)
Abstract:Bisphenol A (BPA) is a monomer of polycarbonate plastics that has estrogenic activities and has been shown to be a substrate for multidrug resistant efflux mechanisms, specifically, P-glycoprotein. Since the natural hormone estrogen reverses multidrug resistance in some cell types, we hypothesized that BPA might have a similar activity in trophoblasts. We have used BeWo cells as an in vitro model for human trophoblasts and calcein AM as a substrate for drug efflux mechanism to characterize BPA interactions with placental P-glycoprotein. We found that chronic exposure of BeWo cells to BPA did not alter intracellular calcein accumulation in a fashion that would be reflective of changes in Pglycoprotein expression. However, BeWo cells acutely exposed to BPA pre-treatment were observed to have a significantly decreased calcein accumulation suggesting a direct stimulatory effect on P-gp. Addition of cyclosporin A, a P-glycoprotein inhibitor and substrate, completely reversed BPA's effects on calcein accumulation and resulted in a net increase, relative to controls, in calcein accumulation by the BeWo cells. BPA was found not stimulate P-gp ATPase. Therefore, our results suggested that BPA stimulated drug efflux by BeWo cells probably by direct effects on P-glycoprotein.