Different aspects of Bisphenol A(BPA) as endocrine disruptor chemical in Human Breast Cancer cells MCF-7

Bisphenol A (BPA) is a common constituent of plastics and a current public health concern. The aim of this study was to explore the effects of BPA exposure using the estrogen-responsive human breast cancer cell line, MCF-7. We exposed MCF-7 cells to BPA and measured several toxicologic endpoints, such as cell viability, proliferation, and apoptosis. BPA equivalently reduced MCF-7 cell viability and proliferation with an IC50 of ~20 µM. DNA fragmentation, an indicator of programmed cell death (apoptosis) was detected after 72 h exposure to 10 µM BPA. The effects of 17ß-estradiol (E2) differed from BPA. E2 caused less apoptosis and its antiproliferative effect varied as a function of glucose concentration in the medium. To define glucose effect on estrogen receptor (ER) and cytokine gene expression against BPA sensitivity, cells were grown in high glucose (4.5 g/L) and low glucose (1.0 g/L) medium and the relative mRNA levels of various cytokines were determined using PCR techniques. BPA treatment increased the relative mRNA of cytokines TGFα, TNFα and IL-6 mRNA fivefold. However relative mRNA of ERα and ERß remained unchanged in high or low glucose conditions. Conversely, Peroxisome Proliferator-Activated Receptor (PPAR) ß mRNA levels increased upon exposure to 10 µM of BPA under high glucose conditions. Our results indicate that while micromolar levels of PBA are directly toxic to estrogen-responsive cells, there are clear differences between the cellular responses to BPA and estrogens.