Bisphenol A Impairs Estradiol-induced Protective Effects Against DLD-1 Colon Cancer Cell Growth

Bisphenol A (BPA), a prototype of endocrine disruptors, mimics 17 beta-estradiol (E2)-induced proliferation in several cancer cells by binding to estrogen receptor alpha (ER alpha). However, scarce and conflicting data are available concerning the effect of BPA on estrogen receptor beta (ER beta)-mediated functions. Here, the detailed analysis of the effect of BPA, alone or in combination with E2, on ER beta-mediated cellular functions is reported in ER beta-expressing colon cancer cell line. BPA binds to ER beta without activating any receptor activities. On the other hand, BPA inhibits E2-induced genomic activity of ER beta as well as ER beta extra-nuclear activities (i.e., ER beta:p38 association and p38 activation). As a consequence, BPA impairs the E2-induced activation of the apoptotic cascade which is at the root of the protective role played by the hormone against colon cancer growth. Thus, women may be considered a highly susceptible population with an increased risk of colon cancers after BPA exposures. (C) 2010 IUBMB IUBMB Life, 62(9): 684-687, 2010