Biomol Ther (Seoul)  
Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation
Ji-wei Ma, Yong Zhang, Ji-cheng Ye, Ru Li, Yu-Lin Wen, Jian-xian Huang and Xue-yun Zhong*
Division of Pathology, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Medical College, Jinan University, Guangzhou 510632, China
E-mail: tzxy@jnu.edu.cn
Tel: +86-20-85228363, Fax: +86-20-85228343
The first three authors contributed equally to this work.
Received: February 25, 2016; Revised: May 21, 2016; Accepted: July 28, 2016; Published online: November 8, 2016.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.
Keywords: Tetrandrine, Glioma, Radiosensitization, Proliferation, ERK


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