Abstract / Summary
Background/Objectives: Lipid metabolism dysregulation contributes to cancer progression. Monoacylglycerol lipase (MAGL) breaks down 2-arachidonoylglycerol (2-AG) into glycerol and arachidonic acid, a substrate for cyclooxygenase-2 (COX-2) to produce pro-inflammatory mediators such as prostaglandin E2 (PGE2). Lipopolysaccharide (LPS) activation of Toll-like receptor 4 (TLR4) triggers inflammatory pathways, including COX-2/PGE2 signaling, implicated in diseases such as melanoma. MAGL inhibition reduces prostaglandins and other inflammatory mediators, but its role in inflammation-driven melanoma progression remains unexplored. This study investigated how JZL184, a selective MAGL inhibitor, and 2-AG affect LPS-induced inflammation, proliferation, and migration in B16 melanoma cells. Methods: Cells received LPS alone or with JZL184 or 2-AG. We measured inflammatory transcripts by qRT-PCR, COX-2 protein by Western blot, PGE2 release by ELISA, proliferation by CCK-8, and migration by scratch assay. Results: LPS increased COX-2, PGE2, VEGF, N-cadherin, and inflammatory cytokine expression. JZL184 suppressed these LPS-induced changes and reduced cell proliferation and migration. In contrast, 2-AG did not alter LPS-induced proliferation or inflammatory signals. JZL184’s effects on inflammatory gene expression and proliferation were independent of CB1 receptor signaling, suggesting its anti-melanoma activity may result from reduced inflammatory mediators rather than enhanced endocannabinoid signaling. Conclusions: These findings provide initial evidence that MAGL may regulate inflammation-triggered melanoma progression and could be a plausible therapeutic target.