TY - JOUR
T1 - Laccase treatment impairs bisphenol A-induced cancer cell proliferation affecting estrogen receptor α-dependent rapid signals
AU - Bolli, Alessandro
AU - Galluzzo, Paola
AU - Ascenzi, Paolo
AU - Del Pozzo, Giovanna
AU - Manco, Immacolata
AU - Vietri, Maria Teresa
AU - Mita, Luigi
AU - Altucci, Lucia
AU - Mita, Damiano Gustavo
AU - Marino, Maria
PY - 2008
Y1 - 2008
N2 - 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 ERα-dependent signal transduction pathways. Similar to 17α-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 ERα-devoid cancer cells, indicating that an ERα-independent mechanism participates to BPA-induced cytotoxicity. On the other hand, BPA oxidation by laccase impairs the binding of this environmental estrogen to ERα loosing at all ERα-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.
AB - 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 ERα-dependent signal transduction pathways. Similar to 17α-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 ERα-devoid cancer cells, indicating that an ERα-independent mechanism participates to BPA-induced cytotoxicity. On the other hand, BPA oxidation by laccase impairs the binding of this environmental estrogen to ERα loosing at all ERα-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.
KW - Bisphenol A
KW - Cell proliferation
KW - Endocrine disruptor
KW - Estrogen receptor α
KW - Laccase-catalyzed inactivation of bisphenol A
UR - http://www.scopus.com/inward/record.url?scp=59649117377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59649117377&partnerID=8YFLogxK
U2 - 10.1002/iub.130
DO - 10.1002/iub.130
M3 - Article
C2 - 18767177
AN - SCOPUS:59649117377
VL - 60
SP - 843
EP - 852
JO - IUBMB Life
JF - IUBMB Life
SN - 1521-6543
IS - 12
ER -