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Oncotarget. 2017 Jul 18;8(29):47425-47439. doi: 10.18632/oncotarget.17659.

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

Author information

1
School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
2
Division of Pediatric Surgery, Department of Surgery, China Medical University Children's Hospital, Taichung, Taiwan.
3
Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
4
Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan.
5
School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
6
Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
7
Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung, Taiwan.
8
Department of Biotechnology, Asia University, Taichung, Taiwan.
9
Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
10
Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.

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.

KEYWORDS:

apoptosis; cervical cancer; p38MAPK; reactive oxygen species; α-mangostin

PMID:
28537893
PMCID:
PMC5564576
DOI:
10.18632/oncotarget.17659
[Indexed for MEDLINE]
Free PMC Article

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