Abstract
We investigated the effects of two natural dietary retinoid X receptor (RXR) ligands, phytanic acid (PA) and docosahexaenoic acid (DHA), on proliferation and on the metabolism of retinol (vitamin A) in both cultured normal human prostate epithelial cells (PrECs) 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 presence of retinol. A synthetic RXR-specific ligand also inhibited PC-3 cell proliferation, whereas all-trans retinoic acid (ATRA) did not. PA and DHA treatment increased the levels of retinyl esters (REs) in both PrECs and PC-3 cells and generated novel REs that eluted on reverse-phase HPLC at 54.0 and 50.5 min, respectively. Mass spectrometric analyses demonstrated that these novel REs were retinyl phytanate (54.0 min) and retinyl docosahexaenoate (50.5 min). Neither PA nor DHA increased LRAT mRNA levels in these cells. In addition, we demonstrate 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.
Highlights
We investigated the effects of two natural dietary retinoid X receptor (RXR) ligands, phytanic acid (PA) and docosahexaenoic acid (DHA), on proliferation and on the metabolism of retinol in both cultured normal human prostate epithelial cells (PrECs) and PC-3 prostate carcinoma cells
Our results indicate that lecithin:retinol acyltransferase (LRAT) catalyzes the esterification of all-trans retinol (ROH) and PA to retinyl phytanate, whereas retinyl docosahexaenoate generated in the presence of DHA and ROH is produced by an enzyme other than LRAT
We conclude that the combination of ROH and either PA or DHA did not result in greater inhibition of cell proliferation than did PA or DHA alone
Summary
We investigated the effects of two natural dietary retinoid X receptor (RXR) ligands, phytanic acid (PA) and docosahexaenoic acid (DHA), on proliferation and on the metabolism of retinol (vitamin A) in both cultured normal human prostate epithelial cells (PrECs) and PC-3 prostate carcinoma cells. A synthetic RXR-specific ligand inhibited PC-3 cell proliferation, whereas all-trans retinoic acid (ATRA) did not. Retinol dehydrogenases oxidize ROH to all-trans retinaldehyde, and all-trans retinaldehyde is further metabolized to all-trans retinoic acid (ATRA) by retinaldehyde dehydrogenases [11]. ROH is converted to all-trans retinyl esters primarily by lecithin:retinol acyltransferase (LRAT), and retinyl esters (REs) are hydrolyzed to retinol by ester hydrolases [9, 13,14,15].
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