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

• Published in: Biochemical and biophysical research communications 2020-07, Vol.527 (4), p.1057-1063
• Main Authors: Ding, Shou-Yong, Wang, Min-tuo, Dai, Da-fei, Peng, Jun-lu, Wu, Wei-lin
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis; Apoptosis - drug effects; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; Glucosides - chemistry; Glucosides - pharmacology; Glucosides - therapeutic use; Hep G2 Cells; Hepatocellular carcinoma; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mice, Inbred BALB C; Mice, Nude; Phenols - chemistry; Phenols - pharmacology; Phenols - therapeutic use; Rhodiola - chemistry; Salidroside
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.05.066

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. [Display omitted] •Salidroside effectively inhibits progression of Hepatocellular carcinoma.•Salidroside delays HCC development by induction of several apoptosis pathway.•ER stress mediates Salidroside-induced anti-HCC activity.