Two α-dicarbonyls downregulate migration, invasion, and adhesion of liver cancer cells in a p53-dependent manner

Dig Liver Dis. 2013 Nov;45(11):938-46. doi: 10.1016/j.dld.2013.05.005. Epub 2013 Sep 23.

Abstract

Background: Hepatocellular carcinoma accounts for more than 600,000 deaths per year due to it being a highly invasive tumor. The α-dicarbonyl, methylglyoxal demonstrates efficacy at reducing tumor burden, however the anti-cancerous activities of 3-deoxyglucosone, have never been studied.

Aims: To determine the anti-cancerous potential of methylglyoxal and 3-deoxyglucosone on liver tumor cells.

Methods: The in vitro effects of methylglyoxal and 3-deoxyglucosone were studied by investigating migration, invasion, and adhesion of Huh-7, HepG2, and Hep3B cells.

Results: 3-Deoxyglucosone inhibited migration of Huh-7 and HepG2 cells. Methylglyoxal decreased migration of HepG2 cells. Additionally, 3-deoxyglucosone and methylglyoxal impaired invasion, and adhesion of Huh-7 and HepG2 cells. In Hep3B cells, a p53 null cell line, 3-deoxyglucosone and methylglyoxal had no effect on migration, invasion, or adhesion. However, both compounds inhibited invasion of wild-type p53 transfected Hep3B cells. Silencing of p53 in Huh-7 and HepG2 cells abrogated the effects of the α-dicarbonyls on cell invasion. 3DG and MG did not alter p53 total protein but promoted nuclear translocation of p53.

Conclusions: These studies suggest that 3-deoxyglucosone and methylglyoxal impair invasion, migration, and adhesion of hepatocellular carcinoma. The effects of both compounds on cell invasion are dependent on p53 and imply that α-dicarbonyls could be efficacious in the treatment of p53-expressing invasive liver tumors.

Keywords: 3-Deoxyglucosone; Adhesion; Invasion; Methylglyoxal; Migration; p53.

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Cell Adhesion / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Deoxyglucose / analogs & derivatives*
  • Deoxyglucose / therapeutic use
  • Down-Regulation / drug effects*
  • Drug Therapy, Combination
  • Genes, p53 / genetics*
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Neoplasm Invasiveness / genetics*
  • Pyruvaldehyde / therapeutic use*

Substances

  • Pyruvaldehyde
  • Deoxyglucose
  • 3-deoxyglucosone