Salidroside induces apoptosis and triggers endoplasmic reticulum stress in human hepatocellular carcinoma

Salidroside possesses excellent anti-tumor activity in many types of malignant tumor. In present study, we focused on the effects of salidroside on hepatocellular carcinoma (HCC). The viability of human HCC cells was assayed using MTT. Apoptosis in the cells and tissues samples were detected by Annexin V/PI or TUNEL staining assays. The levels of apoptosis and endoplasmic reticulum (ER) stress related proteins were measured by western blotting analysis. We found salidroside significantly suppressed cell viability and promoted apoptosis in HCC cells. Salidroside could activate intrinsic and extrinsic apoptotic pathways, by increasing activities of caspase-3, caspase-8 and caspase-9, up-regulating levels of Bax, Cytochrome c and decreasing level of Bcl-2 in HepG2 cells. Moreover, it was found salidroside induced ER stress and increased expression of p-PERK, eIF2a, p-eIF2a, ATF-6 and CHOP in HepG2 cells. Interestingly, knockdown of CHOP impaired salidroside induced inhibitory effects on HepG2 cells, suggesting the important role of ER stress in cytotoxic effect of salidroside. Finally, we have confirmed salidroside induced ER stress and inhibited development of HepG2 in an xenograft mouse model. In conclusion, our data suggest salidroside inhibits viability and induces apoptosis of HCC both in vitro and vivo, and this effect is partially mediated by activation of ER stress.