Magnolol exerts anticancer activity in hepatocellular carcinoma cells through regulating endoplasmic reticulum stress-mediated apoptotic signaling

Ya-Dong Wang,1 Xue-Jun Sun,2 Wei-Jun Yang,3 Jing Li,1 Jia-Jun Yin1 1Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, People’s Republic of China; 2Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China; 3Department of General Surgery, The First People’s Hospital of Guiyang, Guiyang 550002, People’s Republic of China Introduction: Magnolol (Mag), a biologically active compound isolated from the root and stem bark of Magnolia officinalis, has been reported to induce apoptosis in several cancer cell lines in vitro. In the present study, we aimed to determine the anticancer effects of Mag on hepatocellular carcinoma (HCC) cells. Materials and methods: The HepG2 cells were treated with varying concentrations of Mag (10, 20, and 30 µM) for 48 hours. The effects of Mag on the proliferation, migration, invasion, apoptosis and cell cycle progression of HepG2 cells were respectively detected by MTT assay, transwell assays, and flow cytometric analysis. A HepG2 cell-based tumor-bearing model was established to evaluate the effect of Mag on HCC tumor growth in vivo. The protein expression levels were determined by Western blot analysis. Results: Our results showed that Mag inhibited the proliferation, migration, and invasion of HepG2 cells in vitro in a dose-dependent manner. In addition, Mag reduced the HCC tumor volume and weight in the mouse xenograft model. Subsequent studies showed that Mag induced apoptosis in HepG2 cells, accompanied by a loss in mitochondrial membrane potential, cytochrome c release, and induction of endoplasmic reticulum stress. Furthermore, inhibition of the endoplasmic reticulum stress by CHOP knockdown restored the effects of Mag in HepG2 cells. Conclusion: The present study highlighted the possibility of using Mag as a novel therapeutic drug for HCC treatment. Keywords: hepatocellular carcinoma, magnolol, apoptosis, mitochondrial dysfunction, endoplasmic reticulum stres