Journal article
Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells
Toxicology and applied pharmacology, Vol.288(2), pp.232-239
10/15/2015
DOI: 10.1016/j.taap.2015.07.019
PMCID: PMC4587297
PMID: 26220687
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-κB 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-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development.
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•Arsenic is able to induce Cox-2 expression in colorectal cancer cells.•Ethanol, a diet nutritional factor, could enhance arsenic-induced Cox-2.•The up-regulation of Cox-2 via both NFAT and NF-κB activities.
Details
- Title: Subtitle
- Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells
- Creators
- Lei Wang - University of KentuckyJohn Andrew Hitron - University of KentuckyJames T.F Wise - University of KentuckyYoung-Ok Son - University of KentuckyRam Vinod Roy - University of KentuckyDonghern Kim - University of KentuckyJin Dai - University of KentuckyPoyil Pratheeshkumar - University of KentuckyZhuo Zhang - University of KentuckyMei Xu - University of KentuckyJia Luo - University of KentuckyXianglin Shi - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Toxicology and applied pharmacology, Vol.288(2), pp.232-239
- DOI
- 10.1016/j.taap.2015.07.019
- PMID
- 26220687
- PMCID
- PMC4587297
- NLM abbreviation
- Toxicol Appl Pharmacol
- ISSN
- 0041-008X
- eISSN
- 1096-0333
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000009, name: National Institutes of Health, award: R01ES021771, R01ES025515, R01ES020870, R01ES017244
- Language
- English
- Date published
- 10/15/2015
- Academic Unit
- Pathology
- Record Identifier
- 9984201251502771
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