Chemotherapeutic and Immunotherapeutic Effects of 15-deoxy-delta12, 14- prostaglandin J2 on Prostate Cancer

摘要

It has been suggested that compositions of essential fatty acids (EFAs) in diets consumed by humans can largely affect the incident rates of many cancers including prostate cancer. In fact, omega-3 polyunsaturated essential fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and one of their terminal metabolites, 15-deoxy-delta12,l4-prostaglandin J2 (15d-PGJ2) may be involved in cell growth and differentiation. The peroxisome proliferator activated receptors (PPARs) as transcription factors are the mediators for some of these hormone-like lipids. Our aims were to determine the growth responses of human prostate cells to l5d-PGJ2 and related lipids and the role of PPARgamma. Additional study was to investigate the effects of DHA and EPA on androgen receptor mediated action in prostate cancer. We completed these aims. It was found that the expression and functions of PPARgamma were activated by 15d-PGJ2 and DHA. PPARgamma was also detected by western analysis in human prostate cancerous tissues. Moreover, in contrast to other studies with non- prostate cells, we showed that both androgen responsive and -refractory prostate cells are all induced by 15d-PGJ2 and PUFAs to undergo, instead of differentiation into adipocyte-like cells, S-phase cell cycle arrest and non- apoptotic programmed cell death. Interestingly. we discovered that DHA, 15d-PGJ2 and/or EPA- can interfere with androgen receptor's function in human prostate cancer cells. Further studies seem to indicate that these PUFAs can activate an inhibitory cross-talking component, AP-l protein, that interacted with and inhibited androgen receptor's function. Our studies provide a strong basis for the use of these PUFAs as intervening means to prevent or treat prostate cancer.