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 significa ntly enhanced in human skin epidermal cancer cells and that cancer cell gro wth was effectively inhibited by the suppression of COX-2 expression by tra nsfection with COX-2 antisense oligonucleotide. The purpose of this study w as to search for agents which suppress COX-2 expression and examine their e ffects 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? 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 e xpression and PGE2 biosynthesis in a concentration-dependent manner. Cell g rowth was significantly inhibited by 9-cis-RA and PDTC. These results sugge st that 9-cis-RA and PDTC may be useful in preventing skin cancer grow;th a nd that COX-2 is involved in their protective effects on skin carcinogenesi s. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.