Maslinic acid promotes autophagy by disrupting the interaction between Bcl2 and Beclin1 in rat pheochromocytoma PC12 cells

被引:16
|
作者
Dong, Xiaoli [1 ,7 ,8 ]
Zhang, Jiaxiao [2 ]
Zhou, Zhilin [3 ]
Ye, Zhennan [4 ]
Chen, Jiahao [2 ]
Yuan, Jifan [2 ]
Cao, Fengjun [5 ]
Wang, Xuanbin [5 ,6 ]
Liu, Wenchao [1 ]
Yu, Wenxuan [1 ,7 ]
Li, Xiaohua [1 ,2 ]
机构
[1] Hong Kong Polytech Univ, Shenzhen Res Inst, Shenzhen, Peoples R China
[2] Shenzhen Benevop Biomed Co Ltd, Dept Res & Dev, Shenzhen, Peoples R China
[3] Huazhong Univ Sci & Technol, Liyuan Hosp, Dept Gen Surg, Tongji Med Coll, Wuhan, Hubei, Peoples R China
[4] Jena Univ Hosp, Dept Biochem 2, Jena, Germany
[5] Hubei Univ Med, Renmin Hosp, Oncol Ctr, Lab Chinese Herbal Pharmacol, Shiyan, Peoples R China
[6] Hubei Key Lab Wudang Local Chinese Med Res, Shiyan, Peoples R China
[7] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Hong Kong, Hong Kong, Peoples R China
[8] State Key Lab Chinese Med & Mol Pharmacol Incubat, Shenzhen, Peoples R China
基金
中国国家自然科学基金;
关键词
maslinic acid; autophagy; regulation; Beclin1; Bcl2; CANCER CELLS; DERIVATIVES; APOPTOSIS; ANTIOXIDANT; TRITERPENE; DIFFERENTIATION; MITOCHONDRIA; MECHANISMS; COMPLEX;
D O I
10.18632/oncotarget.20210
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Maslinic acid (2 alpha, 3 beta-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.
引用
收藏
页码:74527 / 74538
页数:12
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