Bisphenol A suppresses colon epithelial cell responses via G(0)/G(1)-phase arrest, MAPK and PI3K/AKT pathway modulation, and MMP-2/9 Inhibition by upregulating p21WAF1.

Bisphenol A (BPA) is a non-steroidal endocrine-disrupting chemical compound with applications in the production of epoxy resins and polycarbonates. Accumulating evidence suggests that BPA damages various organs and tissues, including those of the reproductive, immune, and neuroendocrine systems. However, the mechanisms by which BPA affects the intestinal tract have not been fully elucidated. We explored the adverse effects of BPA on human colonic epithelial cells in vitro by performing comprehensive viability, proliferation, invasion, and migration assays on HCT 116 and HCT-8 cells. BPA suppressed the proliferation of both cell types by regulating cell cycle progression and modulating the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/protein kinase B pathways. Furthermore, BPA treatment significantly reduced the induction of matrix metalloproteinases-2 and -9 by inhibiting the binding activity of specificity protein-1, nuclear factor kappa B, and activator protein-1, thereby interfering with cell migration and invasion. This BPA-induced regulation of colonic epithelial cell proliferation, migration, invasion, and MAPK/AKT pathway was reversed by silencing p21WAF1 with siRNA. Collectively, our data indicate that BPA inhibits the proliferation and mobility of human colonic epithelial cells via p21WAF1 induction. This study provides valuable information into the precise mechanisms underlying the adverse effects of BPA on colonic epithelial cells.