The Chemopreventive Effect of Retinoids on Cellular NF-kappa B Activity Induced by NMU and NEU in Human Malignant Keratinocytes / Journal of the Korean Cancer Association, 대한암학회지

ABSTRACT

PURPOSE: Retinoids have been shown to be effective in suppressing tumor development when chemical carcinogens such as N-nitroso-N-methylurea (NMU) and N- nitroso-N-ethylurea (NEU) were used to induce mammary tumors in a variety of animal models. However, the molecular mechanisms associated with the retinoid- mediated chemopreventive process, as linked to transcription factor NF-kappa B activation, for chemoprevention have not been elucidated. The purpose of this study was to determine the implications of NF-kappa B activation on the chemopreventive role of retinoids and their effect on cellular NF-kappa B activity that's induced by known alkylating chemical carcinogens such as NMU and NEU in human transfectant squamous cell carcinoma (SCC-13) cells. MATERIALS AND METHODS: The activity of NF-kappa B, as regulated by chemical carcinogens and retinoids, was determined in cultured human SCC-13 keratinocytes that were transfected with the pNF-kappa B-SEAP-NPT plasmid; this permitted the expression of the secretory alkaline phosphatase (SEAP) reporter gene in response to the NF-kappa B activity, and the plasmid contained the neomycin phosphotransferase (NPT) gene, which confers resistance to geneticin. The reporter enzyme activity was measured using a fluorescence detection assay method. RESULTS: All-trans retinoic acid and 13-cis retinoic acid induced a reduction of NF-kappa B activity up to 64% and 65%, respectively, compared to the control. For the treatment of the human transfectant cells with chemical carcinogens, all-trans retinoic acid (5 mM) and 13-cis retinoic acid (5 mM) downregulated the cellular NF-kappa B activation up to 83% and 85% compared to the NF-kappa B activity that was upregulated by NMU (5 micro M) and NEU (5 micro M), respectively. CONCLUSION: These results suggest that the chemopreventive effect of retinoids may be mediated by the down- regulated activation of NF-kappa B and that retinoids are implicated in the activation of NF-kappa B in human skin cells.