Abstract
OBJECTIVE: Protodioscin (PD), a steroidal saponin, has a diverse pharmacological activity including neuroprotection, male fertility improvement, and cytotoxicity against various cancers cell lines of different origins. However, the effect of PD on hepatocellular carcinoma (HCC) is still unclear. METHODS: Cell viability, colony formation and flow cytometry analysis for apoptosis profile, mitochondrial membrane potential endoplasmic reticulum (ER) expansion were employed to determine the effect of PD against HCC cells. Transient transfection of siRNA, immunofluorescent imaging and immunoprecipitation were used to elucidate the anti-cancer mechanism of PD. The in vivo toxicity and efficacy of PD were assessed by a xenograft mouse model. RESULTS: PD induced apoptosis, loss of mitochondrial membrane potential and ER expansion in HCC cells. Either downregulation of Mfn1 or Bak reversed PD-induced apoptosis and loss of mitochondrial membrane potential. Further analysis revealed that Mfn1 and Bak will form a complex with IP3R to facilitate the transfer of Ca(2+) from ER to mitochondria and apoptosis. In addition, our tumour xenograft model further verifies the in vivo anti-tumour effect of PD. CONCLUSION: Our study sheds light on the understanding of the anti-HCC effects of PD and may open new aspects for the development of novel treatment for human hepatocellular carcinoma.