Corilagin induces the apoptosis of hepatocellular carcinoma cells through the mitochondrial apoptotic and death receptor pathways

Corilagin, a gallotannin, is one of the major active components of many ethnopharmacological plants and exhibits antitumor, anti-inflammatory and antioxidative properties. In recent years, corilagin has provoked much attention due to its antitumor activity, yet the mechanisms attributed to its anticancer actions are largely unknown. In our previous research, our group reported that corilagin could inhibit the proliferation of hepatocellular carcinoma (HCC) cells by inducing G2/M phase arrest. In the present study, observation of the morphological changes showed that corilagin induced the apoptosis of HCC cells as determined by AO/EB and Hoechst 33258 staining assays. Furthermore, flow cytometric analysis was carried out to calculate the apoptotic rate which was 24.1% following treatment with corilagin (37.5 mu M). At the molecular level, mitochondrial membrane potential assay and western blot analysis showed that the mitochondrial transmembrane potential was reduced and the rate of release of cytochrome c was increased, which led to the activation of caspase-9, caspase-3 and cleavage of PARP in the cytoplasm indicating activation of the mitochondrial apoptotic pathway. Moreover, following treatment with corilagin, we noted upregulation of Fas and FasL and activation of caspase-8 which represented activation of the death receptor pathway, and we also observed downregulation of Bcl-2 and survivin which was also attributed to the antitumor effect of corilagin. These results suggest that corilagin significantly induced the apoptosis of HCC cells through both the mitochondrial apoptotic pathway and the death receptor pathway, and corilagin is a potential complementary anticancer herbal drug for HCC therapy.