Abstract

Thioredoxin reductase (TrxR) is often overexpressed in different types of cancer cells including hepatocellular carcinoma (HCC) cells and regarded as a target with great promise for anticancer drug research and development. Here, we have synthesized and characterized nine new designed rhodium(I) N -heterocyclic carbene (NHC) complexes. All of them were effective towards cancer cells, especially complex 1e was more active than cisplatin and manifested strong antiproliferative activity against HCC cells. In vivo anticancer studies showed that 1e significantly repressed tumor growth in an HCC nude mouse model and ameliorated liver lesions in a chronic HCC model caused by CCl 4 . Notably, a mechanistic study revealed that 1e can strongly inhibit TrxR system both in vitro and in vivo . Furthermore, 1e promoted intracellular ROS accumulation, damaged mitochondrial membrane potential , promoted cancer cell apoptosis and blocked the cells in the G1 phase .