MAP30 promotes apoptosis of U251 and U87 cells by suppressing the LGR5 and Wnt/β-catenin signaling pathway, and enhancing Smac expression

被引:18
作者
Jiang, Yilin [1 ]
Miao, Junjie [1 ]
Wang, Dongliang [1 ]
Zhou, Jingru [1 ]
Liu, Bo [1 ]
Jiao, Feng [1 ]
Liang, Jiangfeng [2 ]
Wang, Yangshuo [1 ]
Fan, Cungang [1 ]
Zhang, Qingjun [1 ]
机构
[1] Peking Univ, Peoples Hosp, Dept Neurosurg, 11 Xizhimen South St, Beijing 100044, Peoples R China
[2] Peking Univ, Int Hosp, Dept Neurosurg, Beijing 102206, Peoples R China
基金
中国国家自然科学基金;
关键词
Momordica charantia anti-human immunodeficiency virus protein 30; glioma; apoptosis; leucine-rich-repeat-containing G-protein-coupled receptor 5; Wnt/beta-catenin signaling; second mitochondria-derived activator of caspase; RIBOSOME-INACTIVATING PROTEINS; GOURD MOMORDICA-CHARANTIA; BITTER-MELON; IN-VITRO; COUPLED RECEPTORS; GLIOMA-CELLS; ALPHA-MMC; ANTI-HIV; ANTITUMOR; PROLIFERATION;
D O I
10.3892/ol.2018.8073
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Significant antitumor activity of Momordica anti-human immunodeficiency virus protein of 30 kDa (MAP30) purified from Momordica charantia has been the subject of previous research. However, the effective mechanism of MAP30 on malignant glioma cells has not yet been clarified. The aim of the present study was to investigate the effects and mechanism of MAP30 on U87 and U251 cell lines. A Cell Counting Kit-8 assay, wound healing assay and Transwell assay were used to detect the effects on U87 and U251 cells treated with different concentrations of MAP30 (0.5, 1, 2, 4, 8 and 16 mu M) over different periods of time. Proliferation, migration and invasion of each cell line were markedly inhibited by MAP30 in a dose-and time-dependent manner. Flow cytometry and fluorescence staining demonstrated that apoptosis increased and the cell cycle was arrested in S-phase in the two investigated cell lines following MAP30 treatment. Western blot analysis demonstrated that leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) expression and key proteins in the Wnt/beta-catenin signaling pathway were apparently decreased, whereas second mitochondria-derived activator of caspase (Smac) protein expression significantly increased with MAP30 treatment in the same manner. These results suggest that MAP30 markedly induces apoptosis in U87 and U251 cell lines by suppressing LGR5 and the Wnt/beta-catenin signaling pathway, and enhancing Smac expression in a dose-and time-dependent manner.
引用
收藏
页码:5833 / 5840
页数:8
相关论文
共 47 条
[41]   Mono-PEGylation of Alpha-MMC and MAP30 from Momordica charantia L.: Production, Identification and Anti-Tumor Activity [J].
Sun, Yun ;
Sun, Fenghui ;
Li, Jianlong ;
Wu, Minlu ;
Fan, Xiang ;
Meng, Yanfa ;
Meng, Yao .
MOLECULES, 2016, 21 (11)
[42]   Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152 [J].
Tchoghandjian, A. ;
Souberan, A. ;
Tabouret, E. ;
Colin, C. ;
Denicolai, E. ;
Jiguet-Jiglaire, C. ;
El-Battari, A. ;
Villard, C. ;
Baeza-Kallee, N. ;
Figarella-Branger, D. .
CELL DEATH & DISEASE, 2016, 7 :e2325-e2325
[43]   Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo [J].
Wang, Dongliang ;
Zhou, Jingru ;
Fan, Cungang ;
Jiao, Feng ;
Liu, Bo ;
Sun, Peng ;
Miao, Junjie ;
Zhang, Qingjun .
ONCOLOGY REPORTS, 2014, 31 (01) :41-49
[44]   Structures of New Triterpenoids and Cytotoxicity Activities of the Isolated Major Compounds from the Fruit of Momordica charantia L. [J].
Wang, Xiaojing ;
Sun, Wei ;
Cao, Jiaqing ;
Qu, Haiyan ;
Bi, Xiuli ;
Zhao, Yuqing .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2012, 60 (15) :3927-3933
[45]   Solution structure of anti-HIV-1 and anti-tumor protein MAP30: Structural insights into its multiple functions [J].
Wang, YX ;
Neamati, N ;
Jacob, J ;
Palmer, I ;
Stahl, SJ ;
Kaufman, JD ;
Huang, PL ;
Huang, PL ;
Winslow, HE ;
Pommier, Y ;
Wingfield, PT ;
Lee-Huang, S ;
Bax, A ;
Torchia, DA .
CELL, 1999, 99 (04) :433-442
[46]   Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma [J].
Wick, Wolfgang ;
Chinot, Olivier L. ;
Bendszus, Martin ;
Mason, Warren ;
Henriksson, Roger ;
Saran, Frank ;
Nishikawa, Ryo ;
Revil, Cedric ;
Kerloeguen, Yannick ;
Cloughesy, Timothy .
NEURO-ONCOLOGY, 2016, 18 (10) :1434-1441
[47]   Akt and β-catenin contribute to TMZ resistance and EMT of MGMT negative malignant glioma cell line [J].
Yi, Guo-zhong ;
Liu, Ya-wei ;
Xiang, Wei ;
Wang, Hai ;
Chen, Zi-yang ;
Xie, Si-di ;
Qi, Song-tao .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2016, 367 :101-106