title: Laccase treatment impairs bisphenol A-induced cancer cell proliferation affecting estrogen receptor alpha-dependent rapid signals.
abstract: A wide variety of environmental contaminants exert estrogenic actions in wildlife, laboratory animals, and in human beings through binding to nuclear estrogen receptors (ERs). Here, the mechanism(s) of bisphenol A (BPA) to induce cell proliferation and the occurrence of its bioremediation by treatment with laccase are reported. BPA, highly present in natural world and considered as a model of environmental estrogen action complexity, promotes human cancer cell proliferation via ERalpha-dependent signal transduction pathways. Similar to 17beta-estradiol, BPA increases the phosphorylation of both extracellular regulated kinase and AKT. Specific inhibitors of these kinase completely block the BPA effect on cancer cell proliferation. Notably, high BPA concentrations (i.e., 0.1 and 1 mM) are cytotoxic even in ERalpha-devoid cancer cells, indicating that an ERalpha-independent mechanism participates to BPA-induced cytotoxicity. On the other hand, BPA oxidation by laccase impairs the binding of this environmental estrogen to ERalpha loosing at all ERalpha-dependent effect on cancer cell proliferation. Moreover, the laccase-catalyzed oxidation of BPA reduces the BPA cytotoxic effect. Thus, laccase appears to impair BPA action(s), representing an invaluable bioremediation enzyme.
authors.affiliation: Department of Biology, University Roma Tre, Viale Guglielmo Marconi 446, Roma, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bolli
authors.forename: Paola
authors.initials: P
authors.lastname: Galluzzo
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Del Pozzo
authors.forename: Immacolata
authors.initials: I
authors.lastname: Manco
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Vietri
authors.forename: Luigi
authors.initials: L
authors.lastname: Mita
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.forename: Damiano Gustavo
authors.initials: DG
authors.lastname: Mita
authors.forename: Maria
authors.initials: M
authors.lastname: Marino