Following HNE treatment, the level of downstream phosphorylation of Akt substrates such as glycogen synthase kinase-3-β (GSK3β) was significantly decreased in the hepatocellular carcinoma cell line HepG2, and this effect was shown to be mediated by Michael addition adducts of HNE with His196 and Cys311 of rAkt2 suggesting inhibition of GSK3β peptide binding in the Akt2 substrate binding pocket. This evidence concerns the gene GSK3B and hepatocellular carcinoma.