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


OBJECTIVE
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.
Drexel University College of Medicine, Department of Microbiology and Immunology, Philadelphia, PA, United States.
Lorena
L
Loarca
Sihem
S
Sassi-Gaha
Carol M
CM
Artlett
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects*; D004359:Drug Therapy, Combination; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011765:Pyruvaldehyde / Q000627:therapeutic use*
D011765:Pyruvaldehyde; D003847:Deoxyglucose; C016350:3-deoxyglucosone
3-Deoxyglucosone; Adhesion; Invasion; Methylglyoxal; Migration; p53