Combined effect of fulvestrant and low dose BPA: comparative implications on EMT, apoptosis, and TGF-β1 signaling in HepG2 cells

Abstract

Bisphenol A (BPA) is an endocrine-disrupting chemical utilized in the manufacture of food packaging, dental materials, medical devices, children's toys, and baby products. Numerous studies have indicated the role of BPA in the etiology of many diseases such as diabetes, cardiovascular diseases, obesity, cancer, and chemotherapeutic resistance. However, the effects of BPA- chemotherapeutic combination remain to be investigated in different cell lines. Here, we demonstrate that low dose BPA and fulvestrant (estrogen receptor antagonist) combination synergistically decrease proliferation, promote cell migration and mesenchymal transition, switching from E-cadherin to N-cadherin expression Hepg2 cells. Moreover, we determined that low dose BPA may evoke susceptibility to apoptosis in HepG2 cells. The mechanism underlying these effects has been identified as increased TGF-β1 signaling. Our results provide an experimental basis for evaluating the potential health risks of low-dose BPA for fulvestrant therapy in hepatocytes.