Synthesis and biological evaluation of gold(III) Schiff base complexes for the treatment of hepatocellular carcinoma through attenuating TrxR activity.

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. Increased thioredoxin reductase (TrxR) levels were recently identified as possible prognostic markers for HCC. Here, four gold(III) complexes 1b-4b bearing Schiff base ligands were synthesized, characterized, and screened for antitumor activity against HCC. All complexes triggered significant antiproliferative effects against HCC cells, especially the most active complex 1b induced HepG2 cells apoptosis by activating the endoplasmic reticulum stress (ERS). 1b could clearly inhibit the TrxR activity to elevate reactive oxygen species (ROS), mediate ERS and lead to mitochondrial dysfunction. Notably, treatment of 1b improved the CCl4-induced liver damage in vivo by down-regulation of TrxR expression and inflammation level.