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 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 chemopreventive and anti-proliferative effects of 4-HPR.
Merritt
G
G
New York Hospital Medical Center of Queens, New York, NY, USA.
Aliprandis
E T
ET
Prada
F
F
Rigas
B
B
Kashfi
K
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D017313:Fenretinide / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D007700:Kinetics; D008565:Membrane Proteins; D010703:Phorbol Esters / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D010703:Phorbol Esters; D012333:RNA, Messenger; D012176:Retinoids; D017313:Fenretinide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone