Liver cancer is the fifth most common cause of
cancer death worldwide. The study of more effective anti-
hepatoma drugs is urgently required.
Bufalin has been isolated from a
traditional Chinese medicine and possesses less toxicity to normal cells. However, it has been found to inhibit growth of
cancer cells. In this study, we aimed to investigate the efficacy and mechanism of
bufalin in Huh7, Hep3B and HA22T human
hepatoma cells. The three cell lines were treated with
bufalin, the proliferation was detected by WST-1 assay and cell cycle was detected by flow cytometry analysis. The results showed that
bufalin inhibited the proliferation of
hepatoma cells and regulated the
hepatoma cell death program in a dose- and time-dependent manner without typical features of apoptosis. RT-PCR arrays were used to investigate the autophagy transcriptional response triggered by
bufalin and 13 genes were altered and further confirmed by real-time PCR. The translation levels of selected genes were examined by western blot analysis to reveal the
bufalin-induced autophagy cascade.
Bufalin synergized with the JNK pathway to induce autophagy of
hepatoma cells and is closely associated with the upregulation of TNF, BECN-1, MAPK and ATG8, together with the downregulation of Bcl-2 and Bid. Our study provided a multi-angle evaluation system for anti-
hepatoma pharmacology for pre-clinical
drug investigation. In this case,
bufalin was capable of inducing
hepatoma cell autophagy, suggesting a potential regimen for single or combined
chemotherapy to overcome
hepatoma in clinical practice.