Abstract
Melittin (Mel), a major component of venom of honey bee (Apismellifera), has various biological effects. Recent researches have reported the anti-tumor activity of Mel in various human cancers, including hepatocellular carcinoma (HCC). In this study, we aimed to further discuss the role of Mel in HCC and investigate the correlation of autophagy with the effect of Mel in HCC cells. Methyl thiazolyl tetrazolium (MTT) assay and flow cytometry were used to detect the viability and apoptosis of HCC cells, respectively. To examine the changes of autophagy in HCC cells treated with Mel, transmission electronmicroscope (TEM) and immunofluorescence detection were adopted. Finally, we used western blot method to detect the changes of pivotal proteins in autophagy and mitochondrial apoptotic pathways. The results of MTT assay and flow cytometry revealed that Mel could suppress the cell viability and promote the apoptosis of HCC cells. Autophagy could be induced by the treatment with Mel in HCC cells. The inhibition of autophagy by chloroquine (CQ) contributed to the enhanced anti-tumor effect of Mel, but autophagy induction by RAPA decreased Mel effect in HCC cells. Mel was closely associated with the expression of proteins in mitochondrial apoptotic pathway. In summary, Mel could induce the autophagy of HCC cells, and the autophagy might offer protection against apoptosis in HCC. Mel might suppress the tumor through activating mitochondrial apoptotic pathway.