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Retinoids/Phytanic Acid, DHEA & Human Prostate Ca Cells

#B128 Cell Growth Inhibition and Alteration of Retinoid Metabolism: Multiple Functions of Phytanic Acid and Docohexaenoic Acid in Human Prostate Cancer Cells.

Xiao-Han Tang, Lorraine J. Gudas,

Weill Medical College of Cornell Univ., New York, NY.

Epidemiological and cell culture studies indicate that retinoids (i.e. vitamin A and related compounds) play certain roles in the prevention of prostate cancer and in the inhibition of prostate tumor growth.

Retinoids mainly exert their physiological functions through retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Recently, the importance of RXRs in the prevention of prostate cancer has been demonstrated.

Phytanic acid is a branched-chain, isoprenoid-derived fatty acid, derived from the phytol side chain of chlorophyll.

Phytanic acid is present at high concentrations in dairy products and in dietary ruminant fats. Docosahexaenoic acid (DHA) is a long chain w-3 polyunsaturated fatty acid that is present at high levels in fish oil.

Both phytanic acid and DHA are natural RXR ligands. In this study we investigated the effects of these two dietary RXR ligands (agonists) on the cell growth and retinoid metabolism of cultured human prostate cancer cell lines.

Retinoic acid (RA) treatment for 72 hours and 120 hours did not have a significant effect on the growth of PC-3 cells. However, RA did suppress the proliferation of LNCaP cells, especially after 120 hours.

The specific RXR agonist BMS 188649 inhibited cell proliferation in both cell lines. Meanwhile, both phytanic acid and DHA inhibited the growth of PC-3 and LNCaP cells.

Phytanic acid and retinoic acid synergistically inhibited the growth of both of these prostate cancer cell lines. In addition, Western blot analysis showed that both phyanic acid and DHA decreased cyclin D1 expression in PC-3 cells.

We also examined retinol (vitamin A) metabolism in PC-3 cells treated with phytanic acid and DHA by HPLC. Both phytanic acid and DHA altered the metabolism of retinol.

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.

Frontiers in Cancer Prevention Research, 2003 AACR

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