Inhibition of Monoacylglycerol Lipase Suppresses Lipopolysaccharide-Enhanced Melanoma Proliferation and Migration
- 1Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Abstract
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.
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BibTeX
@article{almutairi2026inhibition,
title = {{Inhibition of Monoacylglycerol Lipase Suppresses Lipopolysaccharide-Enhanced Melanoma Proliferation and Migration}},
author = {Faris Almutairi and Yazeed Alneef and Hussam Albassam and Saad Alobid and Ahlam M. Alhusaini and Dalal Alkhelb and Abdullah S. Alhamed and Mohammed Alqinyah and Ahmed Altuwaijri and Sabry M. Attia},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203255},
url = {https://www.mdpi.com/2072-6694/18/20/3255},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Inhibition of Monoacylglycerol Lipase Suppresses Lipopolysaccharide-Enhanced Melanoma Proliferation and Migration
AU - Faris Almutairi
AU - Yazeed Alneef
AU - Hussam Albassam
AU - Saad Alobid
AU - Ahlam M. Alhusaini
AU - Dalal Alkhelb
AU - Abdullah S. Alhamed
AU - Mohammed Alqinyah
AU - Ahmed Altuwaijri
AU - Sabry M. Attia
PY - 2026
DA - 2026/10/09
JO - Cancers
DO - 10.3390/cancers18203255
UR - https://www.mdpi.com/2072-6694/18/20/3255
AB - 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.
SN - 2072-6694
ER -