The chemopreventive effect of retinoids on cellular NF-kappaB activity induced by NMU and NEU in human malignant keratinocytes.
Cancer Res Treat
; 39(2): 82-7, 2007 Jun.
Article
en En
| MEDLINE
| ID: mdl-19746216
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-kappaB activation, for chemoprevention have not been elucidated. The purpose of this study was to determine the implications of NF-kappaB activation on the chemopreventive role of retinoids and their effect on cellular NF-kappaB activity that's induced by known alkylating chemical carcinogens such as NMU and NEU in human transfectant squamous cell carcinoma (SCC-13) cells. MATERIALS ANDMETHODS:
The activity of NF-kappaB, as regulated by chemical carcinogens and retinoids, was determined in cultured human SCC-13 keratinocytes that were transfected with the pNF-kappaB-SEAP-NPT plasmid; this permitted the expression of the secretory alkaline phosphatase (SEAP) reporter gene in response to the NF-kappaB 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-kappaB 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-kappaB activation up to 83% and 85% compared to the NF-kappaB activity that was upregulated by NMU (5microM) and NEU (5microM), respectively.CONCLUSION:
These results suggest that the chemopreventive effect of retinoids may be mediated by the downregulated activation of NF-kappaB and that retinoids are implicated in the activation of NF-kappaB in human skin cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cancer Res Treat
Año:
2007
Tipo del documento:
Article