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

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. α-Mangostin has been shown to have potent and multiple anticancer activities. Accordingly, we hypothesized that α-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. α-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 α-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, α-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 α-mangostin administration significantly inhibited the growth of inoculated CSC-like SiHa cells and synergically enhanced the antitumor effect of cisplatin. Our findings indicate that α-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 α-mangostin may have clinical potential to improve chemotherapy for cervical cancer by targeting cervical CSC.

• Authors: Hung-Ju Chien, Tsung-Ho Ying, Shu-Ching Hsieh, Chia-Liang Lin, Yung-Luen Yu, Shao-Hsuan Kao, Yi-Hsien Hsieh
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 235 Issue 7-8 Pg. 5590-5601 (07 2020) ISSN: 1097-4652 [Electronic] United States
• PMID: 31960449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• Xanthones
• Cisplatin
• mangostin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Death (drug effects)
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology)
• Female
• HeLa Cells
• Humans
• Mitochondria (drug effects, genetics)
• Neoplastic Stem Cells (drug effects, pathology)
• Signal Transduction (drug effects)
• Uterine Cervical Neoplasms (drug therapy, genetics, pathology)
• Xanthones (pharmacology)