Pterostilbene Inhibits the Growth of Human Esophageal Cancer Cells by Regulating Endoplasmic Reticulum Stress

被引：48

作者：

Feng, Yingtong ^{[1
,3
]}

Yang, Yang ^{[2
]}

Fan, Chongxi ^{[1
]}

Di, Shouyin ^{[1
]}

Hu, Wei ^{[2
]}

Jiang, Shuai ^{[4
]}

Li, Tian ^{[2
]}

Ma, Zhiqiang ^{[1
]}

Chao, Deng ^{[5
]}

Feng, Xiao ^{[5
]}

Xin, Zhenlong ^{[2
]}

Pang, Sainan ^{[6
]}

Li, Xiaofei ^{[1
]}

Yan, Xiaolong ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Tangdu Hosp, Dept Thorac Surg, 1 Xinsi Rd, Xian 710038, Peoples R China

[2] Fourth Mil Med Univ, Dept Biomed Engn, Xian 710032, Peoples R China

[3] 97th Hosp PLA, Dept Cardiothorac Surg, Xuzhou, Peoples R China

[4] Fourth Mil Med Univ, Dept Aerosp Med, Xian 710032, Peoples R China

[5] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiovasc Surg, Xian 710032, Peoples R China

[6] Jiamusi Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Jiamusi, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2016年 / 38卷 / 03期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

Pterostilbene; Endoplasmic reticulum stress; Human esophageal cancer cells; CHOP siRNA; Thapsigargin; ER STRESS; SPECIFICITY PROTEINS; MEDIATED APOPTOSIS; OXIDATIVE STRESS; TUMOR-GROWTH; DEATH; RESVERATROL; SURVIVAL; ACTIVATION; INDUCTION;

D O I：

10.1159/000443071

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background/Aims: Pterostilbene (PTE), a natural dimethylated resveratrol analog from blueberries, is known to have diverse pharmacological activities, including anticancer properties. In this study, we investigated the anticancer activity of PTE against human esophageal cancer cells both in vitro and in vivo and explored the role of endoplasmic reticulum (ER) stress (ERS) signaling in this process. Methods: Cell viability, the apoptotic index, Caspase 3 activity, adhesion, migration, reactive oxygen species (ROS) levels, and glutathione (GSH) levels were detected to explore the effect of PTE on human EC109 esophageal cancer cells. Furthermore, siRNA transfection and a chemical inhibitor were employed to confirm the role of ERS. Results: PTE treatment dose- and time-dependently decreased the viability of human esophageal cancer EC109 cells. PTE also decreased tumor cell adhesion, migration and intracellular GSH levels while increasing the apoptotic index, Caspase 3 activity and ROS levels, which suggest the strong anticancer activity of PTE. Furthermore, PTE treatment increased the expression of ERS-related molecules (GRP78, ATF6, p-PERK, p-eIF2 alpha and CHOP), upregulated the pro-apoptosis-related protein PUMA and downregulated the anti-apoptosis-related protein Bcl-2 while promoting the translocation of cytochrome c from mitochondria to cytosol and the activation of Caspase 9 and Caspase 12. The downregulation of ERS signaling by CHOP siRNA desensitized esophageal cancer cells to PTE treatment, whereas upregulation of ERS signaling by thapsigargin (THA) had the opposite effect. N-Acetylcysteine (NAC), a ROS scavenger, also desensitized esophageal cancer cells to PTE treatment. Conclusions: Overall, the results indicate that PTE is a potent anti-cancer pharmaceutical against human esophageal cancer, and the possible mechanism involves the activation of ERS signaling pathways. Copyright (C) 2016 S. Karger AG, Basel

引用

页码：1226 / 1244

页数：19

共 41 条

[1] Mitochondrial O2-• and H2O2 mediate glucose deprivation-induced cytotoxicity and oxidative stress in human cancer cells [J].

Ahmad, IM ;

Aykin-Burns, N ;

Sim, JE ;

Walsh, SA ;

Higashikubo, R ;

Buettner, GR ;

Venkataraman, S ;

Mackey, MA ;

Flanagan, SW ;

Oberley, LW ;

Spitz, DR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (06) :4254-4263

[2] Novel proteasome-inhibitory syrbactin analogs inducing endoplasmic reticulum stress and apoptosis in hematological tumor cell lines [J].

Anshu, Ashish ;

Thomas, Simmy ;

Agarwal, Puneet ;

Ibarra-Rivera, Tannya R. ;

Pirrung, Michael C. ;

Schoenthal, Axel H. .

BIOCHEMICAL PHARMACOLOGY, 2011, 82 (06) :600-609

[3]

Barillé-Nion S, 2012, ANTICANCER RES, V32, P4225

[4] Vemurafenib Potently Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in BRAFV600E Melanoma Cells [J].

Beck, Daniela ;

Niessner, Heike ;

Smalley, Keiran S. M. ;

Flaherty, Keith ;

Paraiso, Kim H. T. ;

Busch, Christian ;

Sinnberg, Tobias ;

Vasseur, Sophie ;

Iovanna, Juan Lucio ;

Driessen, Stefan ;

Stork, Bjoern ;

Wesselborg, Sebastian ;

Schaller, Martin ;

Biedermann, Tilo ;

Bauer, Juergen ;

Lasithiotakis, Konstantinos ;

Weide, Benjamin ;

Eberle, Juergen ;

Schittek, Birgit ;

Schadendorf, Dirk ;

Garbe, Claus ;

Kulms, Dagmar ;

Meier, Friedegund .

SCIENCE SIGNALING, 2013, 6 (260)

[5] Celastrol decreases specificity proteins (Sp) and fibroblast growth factor receptor-3 (FGFR3) in bladder cancer cells [J].

Chadalapaka, Gayathri ;

Jutooru, Indira ;

Safe, Stephen .

CARCINOGENESIS, 2012, 33 (04) :886-894

[6] RETRACTED: Licochalcone A induces apoptosis through endoplasmic reticulum stress via a phospholipase Cγ1-, Ca2+-, and reactive oxygen species-dependent pathway in HepG2 human hepatocellular carcinoma cells (Retracted Article) [J].

Choi, A-Young ;

Choi, Ji Hyun ;

Hwang, Keun-Young ;

Jeong, Yeon Ju ;

Choe, Wonchae ;

Yoon, Kyung-Sik ;

Ha, Joohun ;

Kim, Sung Soo ;

Youn, Jang Hyun ;

Yeo, Eui-Ju ;

Kang, Insug .

APOPTOSIS, 2014, 19 (04) :682-697

[7] QUANTITATIVE-ANALYSIS OF DOSE-EFFECT RELATIONSHIPS - THE COMBINED EFFECTS OF MULTIPLE-DRUGS OR ENZYME-INHIBITORS [J].

CHOU, TC ;

TALALAY, P .

ADVANCES IN ENZYME REGULATION, 1984, 22 :27-55

[8] Resveratrol induced ER expansion and ER caspase-mediated apoptosis in human nasopharyngeal carcinoma cells [J].

Chow, Shu-Er ;

Kao, Cheng-Heng ;

Liu, Yi-Tong Albert ;

Cheng, Mei-Ling ;

Yang, Ya-Wen ;

Huang, Yao-Kuan ;

Hsu, Chih-Chin ;

Wang, Jong-Shyan .

APOPTOSIS, 2014, 19 (03) :527-541

[9] Pterostilbene is equally potent as resveratrol in inhibiting 12-O-tetradecanoylphorbol-13-acetate activated NFκB, AP-1, COX-2, and iNOS in mouse epidermis [J].

Cichocki, Michal ;

Paluszczak, Jaroslaw ;

Szaefer, Hanna ;

Piechowiak, Adriana ;

Rimando, Agnes M. ;

Baer-Dubowska, Wanda .

MOLECULAR NUTRITION & FOOD RESEARCH, 2008, 52 :S62-S70

[10] Neuronal Apoptosis Induced by Endoplasmic Reticulum Stress Is Regulated by ATF4-CHOP-Mediated Induction of the Bcl-2 Homology 3-Only Member PUMA [J].

Galehdar, Zohreh ;

Swan, Patrick ;

Fuerth, Benjamin ;

Callaghan, Steven M. ;

Park, David S. ;

Cregan, Sean P. .

JOURNAL OF NEUROSCIENCE, 2010, 30 (50) :16938-16948

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