Effect of Dietary Polyunsaturated Fatty Acids on Castration-resistant Pten-null Prostate Cancer
Menée in vitro et à l'aide de modèles murins, cette étude évalue l'effet d'une supplémentation en acides gras polyinsaturés oméga 3 sur un cancer de la prostate résistant à la castration
A common treatment of advanced prostate cancer involves the deprivation of androgens. Despite the initial response to hormonal therapy, eventually all the patients relapse. In the present study, we sought to determine whether dietary polyunsaturated fatty acid (PUFA) affects the development of castration-resistant prostate cancer. Cell culture, patient tissue microarray, allograft, xenograft, prostate-specific Pten knockout and omega-3 desaturase transgenic mouse models in conjunction with dietary manipulation, gene knockdown and knockout approaches were used to determine the effect of dietary PUFA on castration-resistant Pten-null prostate cancer. We found that deletion of Pten increased androgen receptor (AR) expression and Pten-null prostate cells were castration-resistant. Omega-3 PUFA slowed down the growth of castration-resistant tumors, as compared to omega-6 PUFA. Omega-3 PUFA decreased AR protein to a similar extent in tumor cell cytosolic and nuclear fractions, but had no effect on AR mRNA level. Omega-3 PUFA treatment appeared to accelerate AR protein degradation, which could be blocked by proteasome inhibitor MG132. Knockdown of AR significantly slowed down prostate cancer cell proliferation in the absence of androgens. Our data suggests that omega-3 PUFA inhibits castration-resistant prostate cancer in part by accelerating proteasome-dependent degradation of the AR protein. Dietary omega-3 PUFA supplementation in conjunction with androgen ablation may significantly delay the development of castration-resistant prostate cancer in patients compared to androgen ablation alone.
http://carcin.oxfordjournals.org/content/early/2011/12/08/carcin.bgr290.abstract