Oncotarget

Research Papers:

Alpha-mangostin induces apoptosis through activation of reactive oxygen species and ASK1/p38 signaling pathway in cervical cancer cells

Chien-Hsing Lee, Tsung-Ho Ying, Hui-Ling Chiou, Shu-Ching Hsieh, Shiua-Hua Wen, Ruey-Hwang Chou _ and Yi-Hsien Hsieh

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Oncotarget. 2017; 8:47425-47439. https://doi.org/10.18632/oncotarget.17659

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Abstract

Chien-Hsing Lee1,2, Tsung-Ho Ying3,4, Hui-Ling Chiou5, Shu-Ching Hsieh5, Shiua-Hua Wen6, Ruey-Hwang Chou7,8,* and Yi-Hsien Hsieh6,9,10,*

1School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan

2Division of Pediatric Surgery, Department of Surgery, China Medical University Children's Hospital, Taichung, Taiwan

3Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan

4Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan

5School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

6Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan

7Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung, Taiwan

8Department of Biotechnology, Asia University, Taichung, Taiwan

9Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan

10Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan

*These authors contributed equally to this work

Correspondence to:

Ruey-Hwang Chou, email: rhchou@gmail.com

Yi-Hsien Hsieh, email: hyhsien@csmu.edu.tw

Keywords: α-mangostin, apoptosis, reactive oxygen species, p38MAPK, cervical cancer

Received: November 02, 2016     Accepted: April 20, 2017     Published: May 07, 2017

ABSTRACT

Alpha-mangostin, a natural xanthonoid, has been reported to possess the anti-cancer property in various types of human cancer. However, its effects and mechanism of α-mangostin in cervical cancer remain unclear. We found that α-mangostin effectively inhibited cell viability, resulted in loss of mitochondrial membrane potential (MMP), release of cytochrome C, increase of Bax, decrease of Bcl-2, and activation of caspase-9/caspase-3 cascade in cervical cancer cells. Alpha-mangostin elevated the contents of reactive oxygen species (ROS) to activate p38. Disrupting ASK1/p38 signaling pathway by a specific inhibitor of p38, or by the siRNAs against ASK1, MKK3/6, or p38, significantly abolished α-mangostin-induced cell death and apoptotic responses. Moreover, α-mangostin also repressed tumor growth in accordance with increased levels of p-ASK1, p-p38, cleaved-PARP and cleaved-caspase-3 in the tumor mass from the mouse xenograft model of cervical cancer. In the current study, we provided first evidence to demonstrate that dietary antioxidant α-mangostin could inhibit the tumor growth of cervical cancer cells through enhancing ROS amounts to activate ASK1/p38 signaling pathway and damage the integrity of mitochondria and thereby induction of apoptosis in cervical cancer cells.


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