alpha-Mangostin attenuates stemness and enhances cisplatin-induced cell death in cervical cancer stem-like cells through induction of mitochondrial-mediated apoptosis

doi:10.1002/jcp.29489

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24745

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24745

Title:	alpha-Mangostin attenuates stemness and enhances cisplatin-induced cell death in cervical cancer stem-like cells through induction of mitochondrial-mediated apoptosis
Authors:	Chien, HJ;Ying, TH;Hsieh, SC;Lin, CL;Yu, YL;Kao, SH;Hsieh, YH
Keywords:	apoptosis;cervical cancer stem cells;cisplatin;stemness;alpha-mangostin
Date:	2020
Issue Date:	2022-08-09T08:07:19Z (UTC)
Publisher:	WILEY
ISSN:	0021-9541
Abstract:	Cancer stem cells (CSCs) exhibit specific characteristics including decontrolled self-renewal, tumor-initiating, promoting, and metastatic potential, abnormal stemness signaling, and chemotherapy resistance. Thus, targeting CSC is becoming an emerging cancer treatment. alpha-Mangostin has been shown to have potent and multiple anticancer activities. Accordingly, we hypothesized that alpha-mangostin may diminish the stemness and proliferation of CSC-like cervical cancer cells. In our results, comparing to the parent cells, CSC-like SiHa and HeLa cells highly expressed CSC marker Sox2, Oct4, Nanog, CK-17, and CD49f. alpha-Mangostin significantly reduced the cell viability, sphere-forming ability, and expression of the CSC stemness makers of CSC-like cervical cancer cells. Further investigation showed that alpha-mangostin induced mitochondrial depolarization and mitochondrial apoptosis signaling, including upregulation of Bax, downregulation of Mcl-1 and Bcl-2, and activation of caspase-9/3. Moreover, alpha-mangostin synergically enhanced the cytotoxicity of cisplatin on CSC-like SiHa cells by promoting mitochondrial apoptosis and inhibiting the expression of CSC markers. Consistent with in vitro findings, in vivo tumor growth assay revealed that alpha-mangostin administration significantly inhibited the growth of inoculated CSC-like SiHa cells and synergically enhanced the antitumor effect of cisplatin. Our findings indicate that alpha-mangostin can reduce the stemness and proliferation of CSC-like SiHa and HeLa cells and promote the cytotoxicity of cisplatin, which may attribute to the mitochondrial apoptosis activation. Thus, it suggests that alpha-mangostin may have clinical potential to improve chemotherapy for cervical cancer by targeting cervical CSC.
URI:	http://dx.doi.org/10.1002/jcp.29489 https://www.webofscience.com/wos/woscc/full-record/WOS:000508127500001 https://ir.csmu.edu.tw:8080/handle/310902500/24745
Relation:	JOURNAL OF CELLULAR PHYSIOLOGY ,2020 ,v235 ,issue 7-8 ,p5590-5601
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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