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) treat ment of MT-29 human colon cancer cells for 24-72 h significantly inhibited their growth. Using HCT-15 cells, 4-HPR had limited inhibitory effects on c ell proliferation over the same concentration range and time period. The in hibitory effects of 4-HPR on cell growth in HT-29 cells were markedly reduc ed in the presence of exogenously added prostaglandins (PGs), suggesting a possible role for inhibition of PG synthesis as a mechanism for 4-HPR's ant iproliferative effects. Inhibition of PGE(2) 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 chemopr eventive and anti-proliferative effects of 4-HPR. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.