Combination of chloroquine diphosphate and salidroside induces human liver cell apoptosis via regulation of mitochondrial dysfunction and autophagy

Hepatocellular carcinoma (HCC) is the leading cause of cancer-associated death in the world. Chemotherapy remains the primary treatment method for HCC. Despite advances in chemotherapy and modalities, recurrence and resistance limit therapeutic success. Salidroside (Sal), a bioactive component extracted from the rhizome of Rhodiola rosea L, exhibits a spectrum of biological activities including antitumor effects. In the present study, it was demonstrated that Sal could induce apoptosis and autophagy of 97H cells by using CCK-8 assay, transmission electron microscopy (TEM), Hoechst33342 staining, MDC staining, western blotting. Pretreatment with Sal enhanced apoptosis and autophagy via upregulation of expression levels of Bax, Caspase-3, Caspase-9, light chain (LC)3-II and Beclin-1 proteins and downregulation of expression levels of Bcl-2, LC3-I and p62 protein in 97H cells. Furthermore, Sal was demonstrated to inhibit activation of the PI3K/Akt/mTOR signaling pathway and, when combined with autophagy inhibitor chloroquine diphosphate (CQ), increased phosphorylation of PI3K, Akt and mTOR proteins. The combined treatment with Sal and CQ not only decreased Sal-induced autophagy, but also accelerated Sal-induced apoptosis. Therefore, Sal-induced autophagy might serve a role as a defense mechanism in human liver cancer cells and its inhibition may be a promising strategy for the adjuvant chemotherapy of liver cancer.

Automated summary

Hepatocellular carcinoma (HCC) is the leading cause of cancer-associated death worldwide, and chemotherapy is the primary treatment method. Salidroside (Sal), a bioactive component from Rhodiola rosea L, has been shown to induce apoptosis and autophagy in HCC cells. Sal enhances apoptosis and autophagy by regulating the expression of various proteins and inhibits the PI3K/Akt/mTOR signaling pathway. Furthermore, combining Sal with the autophagy inhibitor chloroquine diphosphate (CQ) can decrease Sal-induced autophagy and accelerate Sal-induced apoptosis.