A Comparative Proteomic Analysis of Erinacine A's Inhibition of Gastric Cancer Cell Viability and Invasiveness

被引:34
作者
Kuo, Hsing-Chun [1 ,2 ,3 ,4 ,5 ]
Kuo, Yur-Ren [6 ,7 ,8 ]
Lee, Kam-Fai [9 ]
Hsieh, Meng-Chiao [5 ,10 ]
Huang, Cheng-Yi [5 ]
Hsieh, Yung-Yu [11 ]
Lee, Ko-Chao [12 ]
Kuo, Hsiang-Lan [8 ]
Lee, Li-Ya [13 ]
Chen, Wan-Ping [13 ]
Chen, Chin-Chu [13 ]
Tung, Shui-Yi [11 ,14 ]
机构
[1] Chang Gung Univ Sci & Technol, Dept Nursing, Chiayi, Taiwan
[2] CGUST, Chron Dis & Hlth Promot Res Ctr, Chiayi, Taiwan
[3] Chang Gung Univ Sci & Technol, Coll Human Ecol, Res Ctr Ind Human Ecol, Taoyuan, Taiwan
[4] Chang Gung Univ Sci & Technol, Coll Human Ecol, Res Ctr Chinese Herbal Med, Taoyuan, Taiwan
[5] Chang Gung Mem Hosp, Dept Surg, Div Colon & Rectal Surg, Chiayi, Taiwan
[6] Kaohsiung Med Univ Hosp, Dept Surg, Div Plast Surg, Kaohsiung, Taiwan
[7] Kaohsiung Med Univ, Coll Med, Fac Med, Kaohsiung, Taiwan
[8] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung, Taiwan
[9] Chang Gung Mem Hosp, Dept Pathol, Chiayi, Taiwan
[10] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan, Taiwan
[11] Chang Gung Mem Hosp, Dept Hepatogastroenterol, Chiayi, Taiwan
[12] Chang Gung Univ, Chang Gung Mem Hosp, Kaohsiung Med Ctr, Div Colorectal Surg,Dept Surg,Coll Med, Kaohsiung, Taiwan
[13] GRAPE KING BIO Ltd, Taoyuan, Taiwan
[14] Chang Gung Univ, Coll Med, Taoyuan, Taiwan
关键词
Erinacine A; ROS; FAK; p70S6K; 1433S; MTUS2; MUSHROOM FRUITING BODIES; CYTOCHROME-C RELEASE; ACTIN REORGANIZATION; MEDIATED INHIBITION; ACTIVATION; GROWTH; TESTOSTERONE; APOPTOSIS; PROTEIN; PROSTATE;
D O I
10.1159/000480338
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background / Aims: Erinacine A, isolated from the ethanol extract of the Hericium erinaceus mycelium, has been demonstrated as a new alternative anticancer medicine. Drawing upon current research, this study presents an investigation of the molecular mechanism of erinacine A inhibition associated with gastric cancer cell growth. Methods: Cell viability was determined by Annexin V-FITC/propidium iodide staining and migration using a Boyden chamber assay to determine the effects of erinacine A treatment on the proliferation capacity and invasiveness of gastric cancer cells. A proteomic assay provided information that was used to identify the differentially-expressed proteins following erinacine A treatment, as well as the mechanism of its targets in the apoptotic induction of erinacine A. Results: Our results demonstrate that erinacine A treatment of TSGH 9201 cells increased cytotoxicity and the generation of reactive oxygen species (ROS), as well as decreased the invasiveness. Treatment of TSGH 9201 cells with erinacine A resulted in the activation of caspases and the expression of TRAIL. Erinacine A induction of apoptosis was accompanied by sustained phosphorylation of FAK/AKT/p70S6K and the PAK1 pathways, as well as the generation of ROS. Furthermore, the induction of apoptosis and anti-invasion properties by erinacine A could involve the differential expression of the 14-3-3 sigma protein (1433S) and microtubule-associated tumor suppressor candidate 2 (MTUS2), with the activation of the FAK/AKT/p70S6K and PAK1 signaling pathways. Conclusions: These results lead us to speculate that erinacine A may generate an apoptotic cascade in TSGH 9201 cells by activating the FAK/AKT/p70S6K/PAK1 pathway and upregulating proteins 1433S and MTUS2, providing a new mechanism underlying the anti-cancer effects of erinacine A in human gastric cancer cells. (C) 2017 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:195 / 208
页数:14
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