Xin-Yu Bai1, Yuan-Gui Liu1, Wu Song2, Ying-Ying Li1, Dong-Shun Hou1, Hao-Ming Luo2, Ping Liu1. 1. Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China. 2. College of Basic Medicine, Changchun University of Chinese Medicine, Changchun, China.
Abstract
OBJECTIVES: To investigate the antitumour property of tetrandrine by inducing autophagy and apoptosis in human gastric cancer cells, and to explore the potential molecular mechanisms. METHODS: The antitumour activity of tetrandrine was assessed through MTT assay. Apoptosis was measured by flow cytometry and microscopic examination of cellular morphology. The mitochondrial membrane potential was detected by staining with Rh-123. Induction of autophagy was monitored by transmission electron microscopy observation, using GFP-LC3 transfection. KEY FINDINGS: The results revealed that tetrandrine exhibits significant antitumour activity against gastric human cancer cell and the antigastric tumour activity was depended on inducing autophagy and apoptosis through upregulating the apoptosis-related protein (cleaved PARP, cleaved caspase-3 and cleaved caspase-9) and autophagy-related protein (Beclin-1, LC3-II and p62), and decreasing the phosphorylation of AKT/mTOR, PS6K and P-4EBP1. Adding the inhibitor of autophagy, 3-MA or Baf-A1, increased the viability of tetrandrine-exposed gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by tetrandrine. CONCLUSIONS: These results demonstrated that the antitumour effects of tetrandrine by inducing autophagy and apoptosis involving Akt/mTOR pathway. Thus, tetrandrine may be a promising lead compound to be further developed in future for cancer therapy.
OBJECTIVES: To investigate the antitumour property of tetrandrine by inducing autophagy and apoptosis in humangastric cancer cells, and to explore the potential molecular mechanisms. METHODS: The antitumour activity of tetrandrine was assessed through MTT assay. Apoptosis was measured by flow cytometry and microscopic examination of cellular morphology. The mitochondrial membrane potential was detected by staining with Rh-123. Induction of autophagy was monitored by transmission electron microscopy observation, using GFP-LC3 transfection. KEY FINDINGS: The results revealed that tetrandrine exhibits significant antitumour activity against gastric humancancer cell and the antigastric tumour activity was depended on inducing autophagy and apoptosis through upregulating the apoptosis-related protein (cleaved PARP, cleaved caspase-3 and cleaved caspase-9) and autophagy-related protein (Beclin-1, LC3-II and p62), and decreasing the phosphorylation of AKT/mTOR, PS6K and P-4EBP1. Adding the inhibitor of autophagy, 3-MA or Baf-A1, increased the viability of tetrandrine-exposed gastric cancer cells, which confirmed the role of autophagy played in the gastric cancer cell death induced by tetrandrine. CONCLUSIONS: These results demonstrated that the antitumour effects of tetrandrine by inducing autophagy and apoptosis involving Akt/mTOR pathway. Thus, tetrandrine may be a promising lead compound to be further developed in future for cancer therapy.