Maslinic acid promotes autophagy by disrupting the interaction between Bcl2 and Beclin1 in rat pheochromocytoma PC12 cells
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Xiaoli Dong1,7,8,*, Jiaxiao Zhang2,*, Zhilin Zhou3,*, Zhennan Ye4, Jiahao Chen2, Jifan Yuan2, Fengjun Cao5, Xuanbin Wang5,6, Wenchao Liu1, Wenxuan Yu1,7 and Xiaohua Li1,2
1The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PRC
2Department of Research and Development, Shenzhen Benevop Biomedical Co., Ltd, Shenzhen, PRC
3Department of General Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PRC
4Department of Biochemistry II, Jena University Hospital, Jena, Germany
5Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, PRC
6Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Shiyan, PRC
7Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PRC
8State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen, PRC
*These authors have contributed equally to this work
Xiaohua Li, email: [email protected]
Keywords: maslinic acid, autophagy, regulation, Beclin1, Bcl2
Received: March 22, 2017 Accepted: June 24, 2017 Published: August 05, 2017
Maslinic acid (2α, 3β-dihydroxyolean-12-en-28-oic acid, MA) was isolated from natural plants and showed anti-cancer activity in rat Pheochromocytoma PC12 cells in our previous studies. We now discover that MA disrupts the interaction between Bcl2 and autophagy scaffold protein Beclin1 in the above cell line, leading to the up-regulation of autophagy. We investigated the effect of MA on the interaction between Bcl2 and Beclin1 by biochemical and biophysical methods in combination with autophagy characterization in the above cell line. Our results suggest that MA may serve as an autophagy activator by directly blocking the Bcl2-Beclin1 interaction to release free Beclin1 required for the recruitment of autophagy positive regulators, implying MA may exert its anti-cancer activity by regulating autophagy.
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