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Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-?B signalings in colorectal cancer cells.

ABSTRACT: Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-?B pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-?B pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development.

SUBMITTER: Wang L

PROVIDER: S-EPMC4587297 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells.

Wang Lei L Hitron John Andrew JA Wise James T F JT Son Young-Ok YO Roy Ram Vinod RV Kim Donghern D Dai Jin J Pratheeshkumar Poyil P Zhang Zhuo Z Xu Mei M Luo Jia J Shi Xianglin X

Toxicology and applied pharmacology 20150726 2

Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol e ...[more]

PMID: 26220687

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Dataset Information

Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-?B signalings in colorectal cancer cells.

Publications

Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells.

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