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

被引：33

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

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2017年 / 43卷 / 01期

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

页码：195 / 208

页数：14