Bisphenol A impairs estradiol-induced protective effects against DLD-1 colon cancer cell growth.
Bisphenol A (BPA), a prototype of endocrine disruptors, mimics 17β-estradiol (E2)-induced proliferation in several cancer cells by binding to estrogen receptor α (ERα). However, scarce and conflicting data are available concerning the effect of BPA on estrogen receptor β (ERβ)-mediated functions. Here, the detailed analysis of the effect of BPA, alone or in combination with E2, on ERβ-mediated cellular functions is reported in ERβ-expressing colon cancer cell line. BPA binds to ERβ without activating any receptor activities. On the other hand, BPA inhibits E2-induced genomic activity of ERβ as well as ERβ extra-nuclear activities (i.e., ERβ: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.
Bolli
Alessandro
A
Department of Biology, University Roma Tre, Roma, Italy.
Bulzomi
Pamela
P
Galluzzo
Paola
P
Acconcia
Filippo
F
Marino
Maria
M
D017209:Apoptosis; D001559:Benzhydryl Compounds; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000503:physiopathology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds