Synergistic Anti-tumor Effect of Palmitoylcarnitine and Dasatinib in Liver Cancer

Abstract

Hepatocellular carcinoma (HCC) is the third major cause of cancer-related death worldwide and responds positively to tyrosine kinase inhibitors (TKIs). Dasatinib (Das) is an Src/Abl family kinase and has been successfully utilized in the treatment of various cancers. Cancer cells are known to limit their oxidative phosphorylation to minimize oxidative stress. Palmitoylcarnitine (Pcar) incubation triggers mitochondria-mediated apoptosis in cancer cells by increasing the mitochondrial respiration rate. It stimulates the H2O2 production in cancer cells and thus induces oxidative stress. Thus, considering the above observations, the combined effect of Pcar and Das on HepG2, liver cancer cells has been evaluated in the present study. Results demonstrated that combined exposure to Pcar and dasatinib inhibited cell growth, proliferation, and invasion efficiency of cancerous cells more than single-drug treatment. Further, cells undergo membrane depolarization and caspase-dependent apoptosis upon exposure to combined treatment. In addition, in vivo study showed that Pcar and dasatinib treatment reduced the tumor size in mice more significantly than single-drug treatment. Thus, considering the above remarks, combined therapy of Pcar and dasatinib may serve as a potential candidate in the treatment of liver cancer in human and animal tissues.