Role of omega-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain metastatic-melanomaWritten by: Yvonne M. Denkins, Doty Kempf, Melissa Ferniz, Shilpa Nileshwar, and Dario Marchetti
Department of Comparative Biomedical Sciences, School of Veterinary Medicine Louisiana State University, USA
SynopsisConstitutive expression of cyclooxygenase-2 (COX-2), an inducible enzyme involved in the control of inflammatory reactions and in the catalytic conversion of polyunsaturated fatty acids (PUFA) into prostaglandins, plays a role in the development and progression of epithelial tumors. Though a large body of evidence indicates that omega omega -6 PUFA such as arachidonic acid (AA) promote the growth of tumor cells, omega -3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have been shown to inhibit tumor cell proliferation. We have investigated the effects of omega -3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show 1) that constitutive expression of COX-2 mRNA is up-regulated by TNF-alpha which correlated with increased prostaglandin E2 (PGE2) production, and 2) regulation of both COX-2 mRNA expression and PGE2 production upon incubation with omega -3 and omega -6 PUFA. COX-2 mRNA expression was significantly increased above control levels in cells incubated with AA resulting in increased prostaglandin production in omega -6 stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with either EPA or DHA. Incubation of 70W with AA increased MatrigelTM invasion 2.4-fold whereas incubation with either EPA or DHA resulted in no change in invasive values. Additionally, incubation of 70W cells with PGE2 resulted in a 2.5-fold increase in invasion, whereas exposure to PGE3 significantly decreased invasion. Our results demonstrate that incubation of 70W with either AA or PGE2 significantly increased invasiveness whereas incubation with EPA or DHA down-regulated both COX-2 mRNA and protein expression with a subsequent decrease in MatrigelTM invasion. Taken together, these results indicate that omega -3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.
http://www.jlr.org/cgi/content/abstract/M400474-JLR200v1Linkback:
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Topic: Role of omega-3 polyunsaturated fatty acids and brain metastatic-melanoma (Read 1113 times)