Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells.

ABSTRACT

Monoacylglycerol lipase (MAGL) is involved in the degradation of triacylglycerol. Previous studies have demonstrated that MAGL regulates tumor growth and metastasis via fatty acid networks, and is associated with colorectal cancer. JZL184 is a MAGL inhibitor, which in the present study was administered to colorectal cancer cell lines, resulting in decreased tumor proliferation, increased apoptosis and increased tumor cell sensitivity to 5-fluorouracil. B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein (Bax) are key proteins in apoptosis. The expression levels of Bcl­2/Bax were determined in colorectal cancer cell lines following JZL184 administration, and it was observed that the mRNA and protein expression levels of Bcl­2 were decreased, whereas the expression levels of Bax were increased. These results indicated that JZL184 may induce tumor cell apoptosis by regulating the expression of Bcl­2 and Bax. Epithelial-mesenchymal transition (EMT) is closely associated with metastasis. Administration of JZL184 in various malignant colorectal cancer cell lines suppressed migration and altered the expression of EMT markers; E­cadherin was increased, whereas the expression levels of vimentin and zinc finger protein SNAI1 were decreased. These results suggested that JZL184 was able to regulate the EMT process, in order to control the migration of colorectal cancer cells, particularly in tumors with a stronger metastatic capability. Therefore, in colorectal cancer, MAGL may be considered a potential therapeutic target and JZL184 may be a possible therapeutic agent.