Atractylon induces apoptosis and suppresses metastasis in hepatic cancer cells and inhibits growth in vivo

Background: Hepatic cancer is the most common primary liver malignancy, with high incidence and mortality worldwide. Atractylon is an active constituent isolated from Atractylodes lancea (Thunb.) DC. and Atractylodes chinensis (DC.) Koidz., which proved to have multiple activities. Methods: In this study, we evaluated the antihepatic cancer (HCC) effect of atractylon in vitro and in vivo and investigated its underlying mechanism. Cell proliferation, colony formation, cell apoptosis, migration and invaison and was identified by MTT, crystal violet staining, flow cytometry analysis, and Transwell assay. The Delta Psi m of HepG2 and MHCC97H cells were detected by Rhodamine 123. The ROS level was determined by 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA) method. Protein expression was identified by Western blot analysis. The anti-HCC effect of atractylon in vivo was evaluated by a subcutaneous tumor model. Results: The results suggested that atractylon significantly inhibits the proliferation and promotes apoptosis of hepatic cancer cell lines, including HepG2, SMCC7721, and MHCC97H. Moreover, the results showed that atractylon reduces the mitochondrial membrane potential (Delta Psi m), increases ROS level, inhibits the expression of Bcl-2, and promotes the expression of Bax and cleaved caspase-3, indicating that atractylon induces HCC apoptosis through the mitochondrial apoptotic pathway. Our results also demonstrated that atractylon inhibits migration and invasion of hepatic cancer cells by inhibiting the epithelial-mesenchymal transition (EMT) process and downregulating MMP-2 and MMP-9 expression. In addition, atractylon inhibited the growth of hepatic cancer and showed an inhibition effect on EMT process in vivo. Conclusion: In all, this study suggested that atractylon showed a promising anti-HCC effect with inhibiting proliferation, inducing apoptosis, and blocking invasion in vitro and inhibiting growth in vivo.