Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

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*

Back
to Top