Abstract
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.
MeSH terms
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / metabolism
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Antineoplastic Agents / pharmacology*
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Apoptosis
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Cell Cycle / drug effects
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Cell Division / drug effects
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / metabolism
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Cyclooxygenase 1
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Cyclooxygenase 2
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Dinoprostone / metabolism
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Dose-Response Relationship, Drug
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Down-Regulation*
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Fenretinide / pharmacology*
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Humans
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Isoenzymes / biosynthesis*
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Kinetics
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Membrane Proteins
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Phorbol Esters / metabolism
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Prostaglandin-Endoperoxide Synthases / biosynthesis*
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RNA, Messenger / metabolism
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Retinoids / pharmacology*
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Isoenzymes
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Membrane Proteins
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Phorbol Esters
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RNA, Messenger
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Retinoids
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Fenretinide
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone