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http://hdl.handle.net/10662/20186
Títulos: | Non-genomic action of resveratrol on androgen and oestrogen receptors in prostate cancer: modulation of the phosphoinositide 3-kinase pathway |
Autores/as: | Benitez López, Dixan Agustín Pozo Guisado, Eulalia Clementi, Marisa Castellón, Enrique Fernández Salguero, Pedro María |
Palabras clave: | Resveratrol;Prostate cancer;Cáncer de próstata;PI3K pathway;Vía PI3K;Androgen receptor;Receptor de andrógenos;Oestrogen receptor;Receptor de estrógeno;GSK-3 |
Fecha de publicación: | 2007 |
Editor/a: | Cancer Research UK |
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 uM) 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. |
URI: | http://hdl.handle.net/10662/20186 |
ISSN: | 1532-1827 |
DOI: | 10.1038/sj.bjc.6603755 |
Colección: | DBYBM - Artículos |
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