Inhibitory effects of 9-cis-retinoic acid and pyrrolidinedithiocarbamate on cyclooxygenase (COX)-2 expression and cell growth in human skin squamous carcinoma cells.
We recently demonstrated that the constitutive expression of cyclooxygenase (COX)-2 protein and prostaglandin E(2) (PGE(2)) biosynthesis were significantly enhanced in human skin epidermal cancer cells and that cancer cell growth was effectively inhibited by the suppression of COX-2 expression by transfection with COX-2 antisense oligonucleotide. The purpose of this study was to search for agents which suppress COX-2 expression and examine their effects on cell growth. Since retinoids and antioxidants have been used for chemoprevention of cancers in several tissues, the effects of these agents on COX-2 expression and PGE(2) biosynthesis in skin squamous carcinoma cells were investigated. Treatment with a retinoid (9-cis-retinoic acid (9-cis-RA)) or an antioxidant (pyrrolidinedithiocarbamate (PDTC)) suppressed COX-2 expression and PGE(2) biosynthesis in a concentration-dependent manner. Cell growth was significantly inhibited by 9-cis-RA and PDTC. These results suggest that 9-cis-RA and PDTC may be useful in preventing skin cancer growth and that COX-2 is involved in their protective effects on skin carcinogenesis.
Kanekura
T
T
Department of Dermatology, Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan. takuro1@m2.kufm.kagoshima-u.ac.jp
Higashi
Y
Y
Kanzaki
T
T
D000111:Acetylcysteine / Q000494:pharmacology; D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D015603:Keratinocytes / Q000378:metabolism; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011759:Pyrrolidines / Q000494:pharmacology*; D012176:Retinoids / Q000494:pharmacology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D013859:Thiocarbamates / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D007527:Isoenzymes; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D011759:Pyrrolidines; D012176:Retinoids; D013859:Thiocarbamates; D000077556:Alitretinoin; C020972:pyrrolidine dithiocarbamic acid; D014212:Tretinoin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000111:Acetylcysteine