Hyperforin Inhibits Cell Growth by Inducing Intrinsic and Extrinsic Apoptotic Pathways in Hepatocellular Carcinoma Cells

被引:57
作者
Chiang, I-Tsang [1 ,4 ,5 ]
Chen, Wei-Ting [6 ]
Tseng, Chih-Wei [7 ]
Chen, Yen-Chung [2 ,4 ]
Kuo, Yu-Cheng [8 ]
Chen, Bi-Jhih [9 ]
Weng, Mao-Chi [10 ]
Lin, Hwai-Jeng [11 ,12 ]
Wang, Wei-Shu [3 ,4 ,13 ]
机构
[1] Natl Yang Ming Univ Hosp, Dept Radiat Oncol, Yilan, Taiwan
[2] Natl Yang Ming Univ Hosp, Dept Pathol, Yilan, Taiwan
[3] Natl Yang Ming Univ Hosp, Dept Med, 152 Xinmin Rd, Yilan 260, Yilan County, Taiwan
[4] Natl Yang Ming Univ Hosp, Canc Med Care Ctr, Yilan, Taiwan
[5] Cent Taiwan Univ Sci & Technol, Dept Radiol Technol, Taichung, Taiwan
[6] Kaohsiung Armed Forces Gen Hosp, Zuoying Branch, Dept Psychiat, Kaohsiung, Taiwan
[7] Dalin Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Internal Med, Div Gastroenterol, Chiayi, Taiwan
[8] Show Chwan Mem Hosp, Radiat Oncol, Changhua, Taiwan
[9] Changhua Christian Hosp, Changhua Christian Med Fdn, Dept Lab Med, Changhua, Taiwan
[10] Atom Energy Council, Inst Nucl Energy Res, Taoyuan, Taiwan
[11] Taipei Med Univ, Div Gastroenterol & Hepatol, Dept Internal Med, Coll Med,Sch Med, Taipei, Taiwan
[12] Shuang Ho Hosp, Div Gastroenterol & Hepatol, Dept Internal Med, 901,291 Zhongzheng Rd, New Taipei 23561, Taiwan
[13] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan
关键词
Hepatocellular carcinoma; hyperforin; apoptosis; CYTOCHROME-C RELEASE; CYCLE ARREST; CANCER; ACTIVATION; ANTIDEPRESSANT; MITOCHONDRIA; FLUOXETINE; INDUCTION; INVASION; DNA;
D O I
10.21873/anticanres.11301
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aim of the present study was to investigate the antitumor effect and mechanism of action of hyperforin in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro. Cells were treated with different concentrations of hyperforin for different periods of time. Effects of hyperforin on cell viability, apoptosis signaling, and expression of anti-apoptotic and proliferative proteins [cellular FLICE-like inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia 1(MCL1), and cyclin-D1] were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and western blotting. Hyperforin significantly inhibited cell viability and expression of anti-apoptotic and proliferative proteins. We also found that hyperforin significantly induced accumulation of cells in sub-G(1) phase, loss of mitochondrial membrane potential, and increased levels of active caspase-3, and caspase-8. Taken together, our findings indicate that hyperforin triggers inhibition of tumor cell growth by inducing intrinsic and extrinsic apoptotic pathways in HCC SK-Hep1 cells.
引用
收藏
页码:161 / 167
页数:7
相关论文
共 29 条
[1]   New therapies for hepatocellular carcinoma [J].
Avila, M. A. ;
Berasain, C. ;
Sangro, B. ;
Prieto, J. .
ONCOGENE, 2006, 25 (27) :3866-3884
[2]   Co-Expression of XIAP and Cyclin D1 Complex Correlates with a Poor Prognosis in Patients with Hepatocellular Carcinoma [J].
Che, Yufang ;
Ye, Fei ;
Xu, Ruliang ;
Qing, Haitao ;
Wang, Xinying ;
Yin, Fei ;
Cui, Miao ;
Burstein, David ;
Jiang, Bo ;
Zhang, David Y. .
AMERICAN JOURNAL OF PATHOLOGY, 2012, 180 (05) :1798-1807
[3]  
Chen JH, 2015, ANTICANCER RES, V35, P6685
[4]   Involvement of reactive oxygen species and caspase-dependent pathway in berberine-induced cell cycle arrest and apoptosis in C6 rat glioma cells [J].
Chen, Ting-Ching ;
Lai, Kuang-Chi ;
Yang, Jai-Sing ;
Liao, Ching-Lung ;
Hsia, Te-Chun ;
Chen, Guang-Wei ;
Lin, Jen-Jyh ;
Lin, Hui-Ju ;
Chiu, Tsan-Hung ;
Tang, Yih-Jing ;
Chung, Jing-Gung .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2009, 34 (06) :1681-1690
[5]   Fluoxetine and the mitochondria: A review of the toxicological aspects [J].
de Oliveira, Marcos Roberto .
TOXICOLOGY LETTERS, 2016, 258 :185-191
[6]   Hyperforin inhibits cancer invasion and metastasis [J].
Donà, M ;
Dell'Aica, I ;
Pezzato, E ;
Sartor, L ;
Calabrese, F ;
Della Barbera, M ;
Donella-Deana, A ;
Appendino, G ;
Borsarini, A ;
Caniato, R ;
Garbisa, S .
CANCER RESEARCH, 2004, 64 (17) :6225-6232
[7]   Expression and biological significance of c-FLIP in human hepatocellular carcinomas [J].
Du, Xilin ;
Bao, Guoqiang ;
He, Xianli ;
Zhao, Huadong ;
Yu, Fang ;
Qiao, Qing ;
Lu, Jianguo ;
Ma, Qingjiu .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2009, 28
[8]   Apoptosis: A review of programmed cell death [J].
Elmore, Susan .
TOXICOLOGIC PATHOLOGY, 2007, 35 (04) :495-516
[9]   Mirtazapine Inhibits Tumor Growth via Immune Response and Serotonergic System [J].
Fang, Chun-Kai ;
Chen, Hong-Wen ;
Chiang, I-Tsang ;
Chen, Chia-Chieh ;
Liao, Jyh-Fei ;
Su, Ton-Ping ;
Tung, Chieh-Yin ;
Uchitomi, Yosuke ;
Hwang, Jeng-Jong .
PLOS ONE, 2012, 7 (07)
[10]  
Fleischer B, 2006, INT J ONCOL, V28, P25