Artículos de revistas
Non-genomic action of resveratrol on androgen and oestrogen receptors in prostate cancer: modulation of the phosphoinositide 3-kinase pathway
Fecha
2007-05Registro en:
BRITISH JOURNAL OF CANCER, v.: 96, issue: 10, p.: 1595-1604, MAY 21 2007
0007-0920
Autor
Benítez, Dixan
Pozo Guisado, E.
Clementi, Marisa
Castellón Vera, Enrique
Fernández Salguero, P. M.
Institución
Resumen
Prostate cancer represents a major concern in human oncology and the phytoalexin resveratrol (RES) inhibits growth and
proliferation of prostate cancer cells through the induction of apoptosis. In addition, previous data indicate that in oestrogenresponsive
human breast cancer cells, RES induces apoptosis by inhibition of the phosphoinositide-3-kinase (PI3K) pathway. Here,
using androgen receptor (AR)-positive LNCaP and oestrogen receptor alpha (ERa)-expressing PC-3 prostate tumour cells, we have
analysed whether the antiproliferative activity of RES takes place by inhibition of the AR- or ERa-dependent PI3K pathway. Although
RES treatment (up to 150 mM) decreased AR and ERa protein levels, it did not affect AR and ERa interaction with p85-PI3K.
Immunoprecipitation and kinase assays showed that RES inhibited AR- and ERa-dependent PI3K activities in LNCaP and PC-3,
respectively. Consistently, lower PI3K activities correlated with decreased phosphorylation of downstream targets protein kinase B/
AKT (PKB/AKT) and glycogen synthase kinase-3 (GSK-3). GSK-3 dephosphorylation could be responsible for the decreased cyclin D1
levels observed in both cell lines. Importantly, RES markedly decreased PKB/AKT phosphorylation in primary cultures from human
prostate tumours, suggesting that the mechanism proposed here could take place in vivo. Thus, RES could have antitumoral activity in
androgen-sensitive and androgen-non-sensitive human prostate tumours by inhibiting survival pathways such as that mediated by
PI3K.