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Publication Detail

Title: Cyclooxygenase-2 (COX-2) mediates arsenite inhibition of UVB-induced cellular apoptosis in mouse epidermal Cl41 cells.

Authors: Zuo, Z; Ouyang, W; Li, J; Costa, M; Huang, C

Published In Curr Cancer Drug Targets, (2012 Jul)

Abstract: Inorganic arsenic is an environmental human carcinogen, and has been shown to act as a co-carcinogen with solar ultraviolet (UV) radiation in mouse skin tumor induction even at low concentrations. However, the precise mechanism of its co-carcinogenic action is largely unknown. Apoptosis plays an essential role as a protective mechanism against neoplastic development in the organism by eliminating genetically damaged cells. Thus, suppression of apoptosis is thought to contribute to carcinogenesis. It is known that cyclooxygenase-2 (COX-2) can promote carcinogenesis by inhibiting cell apoptosis under stress conditions; and our current studies investigated the potential contribution of COX-2 to the inhibitory effect of arsenite in UV-induced cell apoptosis in mouse epidermal Cl41 cells. We found that treatment of cells with low concentration (5 μM) arsenite attenuated cellular apoptosis upon UVB radiation accompanied with a coinductive effect on COX-2 expression and nuclear factor-κB (NFκB) transactivation. Our results also showed that the COX-2 induction by arsenite and UVB depended on an NFκB pathway because COX-2 co-induction could be attenuated in either p65-deficient or p50-deficient cells. Moreover, UVB-induced cell apoptosis could be dramatically reduced by the introduction of exogenous COX-2 expression, whereas the inhibitory effect of arsenite on UVB-induced cell apoptosis could be impaired in COX-2 knockdown C141 cells. Our results indicated that COX-2 mediated the anti-apoptotic effect of arsenite in UVB radiation through an NFκB-dependent pathway. Given the importance of apoptosis evasion during carcinogenesis, we anticipated that COX-2 induction might be at least partially responsible for the co-carcinogenic effect of arsenite on UVB-induced skin carcinogenesis.

PubMed ID: 22463588 Exiting the NIEHS site

MeSH Terms: Animals; Apoptosis/drug effects*; Apoptosis/radiation effects*; Arsenites/toxicity*; Carcinogens, Environmental/toxicity*; Cell Line; Cell Transformation, Neoplastic/chemically induced; Cell Transformation, Neoplastic/metabolism; Cell Transformation, Neoplastic/pathology; Cyclooxygenase 2/biosynthesis*; Cyclooxygenase 2/genetics; Dose-Response Relationship, Drug; Enzyme Induction; Epidermis/drug effects*; Epidermis/enzymology; Epidermis/pathology; Epidermis/radiation effects*; Genes, Reporter; Mice; NF-kappa B/genetics; NF-kappa B/metabolism; NFATC Transcription Factors/genetics; NFATC Transcription Factors/metabolism; Neoplasms, Radiation-Induced/chemically induced; Neoplasms, Radiation-Induced/enzymology; Neoplasms, Radiation-Induced/pathology; RNA Interference; Skin Neoplasms/chemically induced; Skin Neoplasms/enzymology; Skin Neoplasms/pathology; Transcription Factor AP-1/genetics; Transcription Factor AP-1/metabolism; Transfection; Ultraviolet Rays*

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