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Metabolism of anandamide by COX-2 is necessary for endocannabinoid-induced cell death in tumorigenic keratinocytes.
Mol Carcinog. 2009 Aug; 48(8):724-32.MC

Abstract

Nonmelanoma skin cancer is the most prevalent cancer in the United States with approximately 1.25 million new cases diagnosed each year. Cyclooxygenase-2 (COX-2) expression is commonly elevated in these and other epithelial tumors. Cyclooxygenases metabolize arachidonic acid to prostaglandins, which promote growth and survival of tumor cells. COX-2 also metabolizes endocannabinoids forming prostaglandin-ethanolamides (PG-EA); however, the role of these lipid molecules in tumor cell survival is unclear. The goal of this research is to determine if the metabolic products of COX-2 contribute to endocannabinoid-induced cell death. Anandamide [also known as arachidonyl ethanolamide (AEA)] induced cell death in the COX-2 overexpressing squamous carcinoma cell line JWF2. In contrast, AEA did not initiate cell death in HaCaT keratinocytes, which express low basal levels of COX-2. Resistance to AEA-mediated cell death in HaCaT cells was reversed by overexpressing COX-2 in these cells. Next, ELISA assays were carried out to identify prostaglandins involved in AEA-mediated cell death. D-type prostaglandins were predominantly formed in AEA-exposed JWF2 cells although significant increases in E- and F-type prostaglandins were also seen. Cells were then treated with various prostaglandins or PG-EA to determine the contribution of each to AEA-induced cell death. PGD(2) and PGD(2)-EA were found to be cytotoxic to JWF2 keratinocytes and the PGD(2) dehydration products, PGJ(2) and 15-deoxy Delta(12,14) PGJ(2), were also potent inducers of cell death. These results suggest that AEA selectively induces cell death in tumorigenic keratinocytes due to COX-2 overexpression and the resulting metabolism of AEA to cytotoxic prostaglandins.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, East Carolina University, Brody School of Medicine, Greenville, North Carolina 28590, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19148897

Citation

Van Dross, Rukiyah T.. "Metabolism of Anandamide By COX-2 Is Necessary for Endocannabinoid-induced Cell Death in Tumorigenic Keratinocytes." Molecular Carcinogenesis, vol. 48, no. 8, 2009, pp. 724-32.
Van Dross RT. Metabolism of anandamide by COX-2 is necessary for endocannabinoid-induced cell death in tumorigenic keratinocytes. Mol Carcinog. 2009;48(8):724-32.
Van Dross, R. T. (2009). Metabolism of anandamide by COX-2 is necessary for endocannabinoid-induced cell death in tumorigenic keratinocytes. Molecular Carcinogenesis, 48(8), 724-32. https://doi.org/10.1002/mc.20515
Van Dross RT. Metabolism of Anandamide By COX-2 Is Necessary for Endocannabinoid-induced Cell Death in Tumorigenic Keratinocytes. Mol Carcinog. 2009;48(8):724-32. PubMed PMID: 19148897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolism of anandamide by COX-2 is necessary for endocannabinoid-induced cell death in tumorigenic keratinocytes. A1 - Van Dross,Rukiyah T, PY - 2009/1/17/entrez PY - 2009/1/17/pubmed PY - 2009/8/19/medline SP - 724 EP - 32 JF - Molecular carcinogenesis JO - Mol Carcinog VL - 48 IS - 8 N2 - Nonmelanoma skin cancer is the most prevalent cancer in the United States with approximately 1.25 million new cases diagnosed each year. Cyclooxygenase-2 (COX-2) expression is commonly elevated in these and other epithelial tumors. Cyclooxygenases metabolize arachidonic acid to prostaglandins, which promote growth and survival of tumor cells. COX-2 also metabolizes endocannabinoids forming prostaglandin-ethanolamides (PG-EA); however, the role of these lipid molecules in tumor cell survival is unclear. The goal of this research is to determine if the metabolic products of COX-2 contribute to endocannabinoid-induced cell death. Anandamide [also known as arachidonyl ethanolamide (AEA)] induced cell death in the COX-2 overexpressing squamous carcinoma cell line JWF2. In contrast, AEA did not initiate cell death in HaCaT keratinocytes, which express low basal levels of COX-2. Resistance to AEA-mediated cell death in HaCaT cells was reversed by overexpressing COX-2 in these cells. Next, ELISA assays were carried out to identify prostaglandins involved in AEA-mediated cell death. D-type prostaglandins were predominantly formed in AEA-exposed JWF2 cells although significant increases in E- and F-type prostaglandins were also seen. Cells were then treated with various prostaglandins or PG-EA to determine the contribution of each to AEA-induced cell death. PGD(2) and PGD(2)-EA were found to be cytotoxic to JWF2 keratinocytes and the PGD(2) dehydration products, PGJ(2) and 15-deoxy Delta(12,14) PGJ(2), were also potent inducers of cell death. These results suggest that AEA selectively induces cell death in tumorigenic keratinocytes due to COX-2 overexpression and the resulting metabolism of AEA to cytotoxic prostaglandins. SN - 1098-2744 UR - https://www.unboundmedicine.com/medline/citation/19148897/Metabolism_of_anandamide_by_COX_2_is_necessary_for_endocannabinoid_induced_cell_death_in_tumorigenic_keratinocytes_ L2 - https://doi.org/10.1002/mc.20515 DB - PRIME DP - Unbound Medicine ER -