jzl-184 and Adenocarcinoma

Abnormal lipid metabolism plays a dual role in tumorigenesis, specifically in the occurrence and development of cancers. Monoacylglycerol lipase (MAGL), a hydrolase that is important for lipid metabolism, plays a vital role in different aspects of tumorigenesis. Many studies have shown that MAGL is highly elevated in a variety of cancers and plays an active role. However, its potential role in supporting endometrial cancer (EC) growth and progression has not yet been explored in depth.. Immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction were performed to estimate the protein and messenger RNA (mRNA) levels of MAGL in tumor tissues. Then, JZL184 and small interfering RNA (siRNA) were used to decrease the expression of MAGL in EC cells. The gene and protein expression levels of MAGL were measured using quantitative real-time PCR and western blotting, respectively. Additionally, the effect of MAGL on tumor growth in EC was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide , cell cycle and western blotting assay in vitro.. We found that MAGL was overexpressed in EC and was significantly correlated with surgical-pathological stage, myometrial invasion, number of pregnancies and body mass index. The growth and cell cycle progression of tumor cells were significantly impaired in vitro by the pharmacological and siRNA-mediated MAGL inhibition. In addition, MAGL inhibition seemed to repress two target genes, Cyclin D1 and Bcl-2.. In summary, we have demonstrated that MAGL is involved in EC growth and progression. Our results suggest that targeting MAGL may be a novel and valid treatment for EC.

Topics: Adenocarcinoma; Adult; Aged; Benzodioxoles; Cell Cycle; Cyclin D1; Drug Screening Assays, Antitumor; Endometrial Neoplasms; Female; Humans; Middle Aged; Molecular Targeted Therapy; Monoacylglycerol Lipases; Piperidines; Proto-Oncogene Proteins c-bcl-2

Earlier reports suggest that the endocannabinoids may play a role of endogenous tumor growth modulators. In this study, we investigated whether inhibition of the enzymes involved in the synthesis and degradation of endocannabinoids may reduce colorectal cancer cell invasion and migration. The human colon adenocarcinoma Colo-205 cells were incubated with PF-3845, JZL-184 and RHC-80267 (fatty acid amide hydrolase (FAAH), mono- (MAGL) and diacylglycerol lipase (DAGL) inhibitors, respectively) for 48 h. The MTT colorimetric assay was performed to quantify cell viability. Next, Colo-205 cells were incubated with PF-3845 alone or with PF-3845 together with selected antagonists: AM 251, AM 630, SB 366791, RN 1734 and G-15 (CB

Topics: Adenocarcinoma; Amidohydrolases; Antineoplastic Agents; Benzodioxoles; Cell Line, Tumor; Cell Movement; Cell Survival; Colonic Neoplasms; Cyclohexanones; Enzyme Inhibitors; Humans; Piperidines; Pyridines; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2