Submitted on September 21, 2006
Revised on October 23, 2006
Accepted on October 25, 2006
Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid
Xiao-Han Tang, Moo-Jin Suh, Rong Li, and Lorraine J. Gudas
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021
Corresponding Author: ljgudas{at}med.cornell.edu
We investigated the effects of two natural dietary, retinoid X receptor (RXR) ligands, phytanic acid (PA) and docosahexaenoic acid (DHA), on proliferation and on metabolism of retinol (vitamin A) in both cultured normal human prostate epithelial cells (PrEC) and PC-3 prostate carcinoma cells. PA and DHA inhibited the proliferation of the parental PC-3 cells and PC-3 cells engineered to overexpress human lecithin:retinol acyltransferase (LRAT) in both the absence and the presence of retinol. A synthetic RXR-specific ligand also inhibited PC-3 cell proliferation, while all-trans retinoic acid (ATRA) did not. PA and DHA treatment increased the levels of retinyl esters (REs) in both PrEC and PC-3 cells and generated novel REs which eluted on reverse-phase HPLC at 54.0 and 50.5min, respectively. Mass spectrometric analyses demonstrated that these novel REs were retinyl phytanate (54.0min) and retinyl docosahexaenoate (50.5min). Neither PA nor DHA increased LRAT mRNA levels in these cells. In addition, we demonstrated that retinyl phytanate was generated by LRAT in the presence of PA and retinol; however, retinyl docosahexaenoate was produced by another enzyme in the presence of DHA and retinol.
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