A novel quinolinylmethyl substituted ethylenediamine compound exerts anti-cancer effects via stimulating the accumulation of reactive oxygen species and NO in hepatocellular carcinoma cells

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Owing to the limitations in the current therapeutic strategies for treating HCC, development of novel chemotherapeutic drugs is urgently needed. In the present study, we found that QQM, a newly-synthesized quinolinylmethyl substituted ethylenediamine compound, exhibited anti-HCC effects both in vitro and in vivo. QQM inhibited HCC cell growth and induced G0/G1-phase cell cycle arrest and apoptosis in a dose-dependent manner. Our results showed that QQM acted by significantly increasing intracellular reactive oxygen species in HCC cells, which led to cell apoptosis and growth inhibition. Furthermore, QQM treatment resulted in an accumulation of reactive nitric oxide (NO) in HCC cells, and introduction of a NO scavenger, carboxy-PTIO, largely attenuated QQM-induced cytotoxicity. Finally, we found that QQM inhibited growth and induced apoptosis of HCC xenograft tumors in vivo. Taken together, our results indicated that QQM exerted anti-HCC effects by inducing reactive oxygen species and NO accumulation in HCC cells. Thus, QQM exhibits the qualities of a novel, promising anti-tumor candidate for the treatment of HCC.