Activation of Retinold X Receptors by Phytanic acid and Docohexaenoic Acid: Role in the Prevention and Therapy of Prostate Cancer
Annual summary rept. 1 Jan 2004-31 Dec 2005
CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
Pagination or Media Count:
In this study we investigated the effects of two dietary RXR agonists, phytanic acid, and docohexaenoic acid DHA, on the cell growth and retinoid metabolism of cultured normal human prostate epithelial cell PrEC and human prostate cancer cell lines, PC-3 and LNCaP. Both phytanic acid and DHA inhibited the growth of PC-3 and LNCaP cells and decreased cyclin D1 expression in PC-3 cells. Phytanic acid or DHA altered the metabolism of retinol and generated a novel retinyl ester peak. Mass spectrometry analyses demonstrated the novel retinyl ester peak generated by phytanic acid or DHA was retinyl phytanate or retinyl docosahexaenate, respectively. Real time RT-PCR results showed that both phytanic acid and DHA did not dramatically change LRAT expression level in both cell lines. In addition, LRAT participates in the generation of retinyl phytanate, while the generation of retinyl docosahexaenate by DHA is possibly through another different mechanism other than lecithinretinol acyltransferase LRAT and acyl CoAretinol acyltransferase ARAT. These results suggest that both phytantic acid and DHA, natural dietary RXR ligands, may be useful agents for future dietary preventive and therapeutic approaches to human prostate cancer.
- Medicine and Medical Research