RETINOIDS INHIBIT PROTEIN-KINASE C-DEPENDENT TRANSDUCTION OF 1,2-DIGLYCERIDE SIGNALS IN HUMAN COLONIC TUMOR-CELLS

1,2-Diglycerides with long-chain fatty acid residues related to nutrit ional fat (LCDGs) specifically affect growth and urokinase secretion i n human colonic tumor cells, but not in normal mucosa. This allows the m to advance and enhance carcinogenesis in the colon and rectum. SW480 colon carcinoma cells are LCDG sensitive in the same way as primary c olonic tumor cells and have therefore been used as a model system to s tudy the mechanism of LCDG action and to search for inhibitors of tumo r development in the colon. Using this model system, we have shown tha t the effects of LCDGs are transmitted by protein kinase C and abolish ed by downregulation of the enzyme. Retinol, retinoic acid, and beta-c arotene in nanomolar concentrations inhibit LCDG-induced growth and ur okinase secretion and block stimulation of protein kinase C. Although retinol and retinoic acid at higher concentrations also display stimul atory activity, beta-carotene does not. At 100 nM, a concentration tha t can easily be reached in the plasma of humans, beta-carotene reduces LCDG-induced urokinase secretion about 50%. Inasmuch as beta-carotene does not have side effects due to intrinsic activities and storage ef fects, beta-carotene and foods rich in carotenes could be useful in th e prevention of colorectal cancer.