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Two α-dicarbonyls downregulate migration, invasion, and adhesion of liver cancer cells in a p53-dependent manner
Journal article   Open access   Peer reviewed

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

Lorena Loarca, Sihem Sassi-Gaha and Carol M Artlett
Digestive and liver disease, v 45(11), pp 938-946
Nov 2013
DOI: https://doi.org/10.1016/j.dld.2013.05.005
PMID: 24071451
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://arxiv.org/abs/1706.03096View
SubmittedOpen Access (License Unspecified),  Open

Abstract

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
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. To determine the anti-cancerous potential of methylglyoxal and 3-deoxyglucosone on liver tumor cells. The in vitro effects of methylglyoxal and 3-deoxyglucosone were studied by investigating migration, invasion, and adhesion of Huh-7, HepG2, and Hep3B cells. 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. 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.

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Web of Science research areas
Gastroenterology & Hepatology
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