Downregulation of saturated fatty acid and upregulation of unsaturated fatty acid by 13-cis-retinoic acid in human prostate cancer cells.
Retinoids play a major role in regulation of epithelial cell growth and cellular differentiation, but their mechanism(s) of action are still unclear. In the present study, we examined the effects of 13-cis-retinoic acid (13-cis-RA) on cytotoxicity, growth properties, morphology, neutral lipids, phospholipids and fatty acids in cultured human prostate cancer cell lines. The results of these experiments suggest that 13-cis-RA (10 microM) inhibits the DNA synthesis and nude mice tumorigenicity by 2- to 3-fold, compared to control. Electron microscopy revealed more differentiated phenotypes after 13-cis-RA treatment. There was a significant increase in phosphatidylcholine and decrease in sphingomyelin in 13-cis-RA treated cells compared to control. The saturated fatty acids significantly decreased whereas unsaturated fatty acids were increased after 13-cis-RA treatment in prostate cancer cells. This study demonstrates for the first time that retinoic acid mediated downregulation of saturated fatty acids and upregulation of unsaturated fatty acid in human prostate cancer cells.
Dahiya
R
R
Department of Urology, University of California, School of Medicine, San Francisco.
Park
H D
HD
Cassafer
G
G
Cusick
J
J
Narayan
P
P
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D015474:Isotretinoin