Evaluation of Cytotoxicity and Apoptosis Induced by Coumarin Hydrazide-Hydrazone Derivatives in Human Hepatocellular Carcinoma Cell Line

Abstract

Coumarin and aryl hydrazide-hydrazone have attracted our attention due to their vast biological properties. Previous studies suggested that coumarin-tethered aryl hydrazide-hydrazone showed potent activities against HepG2. In the present study, we investigated the cytotoxic potency of the coumarin derivatives 1-3 to compare with coumarin hydrazine-hydrazone hybrids 4 and 5 against hepatocellular carcinoma HepG2 and LH86 cell lines. Among the tested coumarins, hybrids 4 and 5 showed highly potent activity against HepG2 with IC50 values of 17.82 ± 2.79 and 7.87 ± 0.88 µg/mL, respectively. The hybrid 4 also showed the strongest activity against LH86 cell line with IC50 values of 48.32 ± 2.64 µg/mL. Further, we have studied the mechanism of action of the hybrid compounds 4 and 5 in HepG2 cells via the flow-cytometry analysis and the activation of the caspase-3 and caspase-7. The results showed that hybrids 4 and 5 obviously inhibited the proliferation of HepG2 cell line through inducing apoptosis.