arachidonyl-2-chloroethylamide and Liver-Neoplasms

Cancer is a disease characterized by abnormal growth of cells. One of the most common types of liver cancers is called hepatocellular carcinoma (HCC) which is highly metastatic. As most of cannabinoids have shown anticancer effect against different cell lines in a number of reports, a biological investigation of two cannabinoids, CB65 (CB2 receptor agonist) and ACEA (CB1 receptor agonist) was carried out in this study.. In an attempt to find natural products as a new solution of cancer, this study was designed to investigate the potential antitumoral and anti-invasive activity of cannabinoids on HepG2 cells and the possible roles of matrix metalloproteinase-2 (MMP-2) and MMP-9 in its action.. The researchers examined the effect of various concentrations of CB65 (CB2 receptor agonist) and ACEA (CB1 receptor agonist), on the cell proliferation, viability, and invasion as well as expression of MMP-2 and MMP-9 in HepG2 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay, matrigel invasion assay, and western blotting method.. The results revealed that both cannabinoids reduce cell viability, cell invasion as well as MMP-2 and MMP-9 expression in higher dose of 20 nM. Furthermore, higher concentrations of examined cannabinoids were more effective.. These data suggest ACEA and CB65 as an option for novel treatment of hepatocellular cancer.. Our findings may contribute to design of new therapeutic strategies for the management of HCC.

Topics: Antineoplastic Agents; Arachidonic Acids; Cannabinoids; Carcinoma, Hepatocellular; Cell Proliferation; Cell Survival; Drug Screening Assays, Antitumor; Hep G2 Cells; Humans; Liver Neoplasms; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2

Previous studies have indicated the antitumoral effect of human melanocytes, human melanoma cell lines expressing CB1 receptor (CB1), and of the peritumoral administration of endocannabinoids. In the present study, we systematically screened several human melanoma cell lines for the expression of CNR1 and demonstrated transcription of the authentic gene. The product of CNR1, the CB1 protein, was found localized to the cell membrane as well as to the cytoskeleton. Further, the studied human melanoma cell lines expressed functional CB1 since physiological and synthetic ligands, anandamide (AEA), Met-F-AEA, ACEA and AM251 showed a wide range of biological effects in vitro, for example anti-proliferative, proapoptotic and anti-migratory. More importantly, our studies revealed that systemic administration of a stable CB1 agonist, ACEA, into SCID mice specifically inhibited liver colonization of human melanoma cells. Since therapeutic options for melanoma patients are still very limited, the endocannabinoid-CB1 receptor system may offer a novel target.

Topics: Animals; Apoptosis; Arachidonic Acids; Base Sequence; Cannabinoids; Cell Line, Tumor; Cell Movement; Cell Proliferation; Drug Delivery Systems; Endocannabinoids; Humans; Ligands; Liver Neoplasms; Melanoma; Mice; Mice, SCID; Microscopy, Fluorescence; Molecular Sequence Data; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Receptor, Cannabinoid, CB1; Xenograft Model Antitumor Assays