Evaluation of anti-invasion effect of cannabinoids on human hepatocarcinoma cells

Toxicol Mech Methods. 2013 Feb;23(2):120-6. doi: 10.3109/15376516.2012.730559. Epub 2012 Oct 19.


Context: 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.

Objective: 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.

Materials and methods: 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.

Results: 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.

Discussion: These data suggest ACEA and CB65 as an option for novel treatment of hepatocellular cancer.

Conclusion: Our findings may contribute to design of new therapeutic strategies for the management of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Arachidonic Acids / pharmacology*
  • Cannabinoids / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / secondary
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / agonists
  • Receptor, Cannabinoid, CB2 / metabolism


  • Antineoplastic Agents
  • Arachidonic Acids
  • Cannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • arachidonyl-2-chloroethylamide
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • 1,1-dimethylbutyl-1-deoxy-Delta(9)-THC