The retinoid fenretinide inhibits proliferation and downregulates cyclooxygenase-2 gene expression in human colon adenocarcinoma cell lines

Fenretinide [N-(4-Hydroxyphenyl)retinamide, 4-HPR] (10^-10-10^-6 M) treatment of HT-29 human colon cancer cells for 24-72 h significantly inhibited their growth. Using HCT-15 cells, 4-HPR had limited inhibitory effects on cell proliferation over the same concentration range and time period. The inhibitory effects of 4-HPR on cell growth in HT-29 cells were markedly reduced in the presence of exogenously added prostaglandins (PGs), suggesting a possible role for inhibition of PG synthesis as a mechanism for 4-HPR's antiproliferative effects. Inhibition of PGE₂ production was caused by 4-HPR in a concentration-dependent manner and decreased COX-2 but not COX-1 mRNA levels; this is the first indication that 4-HPR selectively inhibits COX-2 gene expression. Our findings suggest a possible mechanism for the chemopreventive and anti-proliferative effects of 4-HPR.