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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

The anti-tumor activity of diosgenin, a new steroidal constituent present in fenugreek, on two human breast cancer cell lines, MCF-7 and Hs578T, was studied. Diosgenin treatment resulted in cell growth inhibition, cell cycle arrest, and apoptosis in concentration- and time-dependent manners in both cell lines. Western blot analyses of whole cell lysates for cell cycle proteins showed that diosgenin altered phosphorylated cyclin checkpoint1 (p-Chk1Ser345) and cyclin B expression, which resulted in G2/M phase blockade. Mechanistically, Cdc25C-Cdc2 signaling was involved in inactivating Chk1Ser345 by p53-dependence in MCF-7 cells and p21-dependence in Hs578T cells that are p53-deficient. Moreover, diosgenin induced a significant loss of the mitochondrial membrane potential in breast cancer cells, and prominently affected cell death through down-regulation of the anti-apoptotic protein, Bcl-2. This released cytochrome c and activated the caspase signaling cascade. Taken together, these findings reveal that the anti-proliferative activity of diosgenin involves the induction of G2/M phase arrest via modulating the Cdc25C-Cdc2-cyclin B pathway and mitochondria-mediated apoptosis in human breast cancer cell lines. This suggests the potential usefulness of diosgenin in treating breast cancer.

Details

Title
Induction of G2/M Phase Arrest by Diosgenin via Activation of Chk1 Kinase and Cdc25C Regulatory Pathways to Promote Apoptosis in Human Breast Cancer Cells
Author
Wen-Ling, Liao 1 ; Jing-Yi, Lin 2 ; Jia-Ching Shieh 3 ; Hsiao-Fong Yeh 2 ; Yi-Hsien Hsieh 2   VIAFID ORCID Logo  ; Yu-Chun, Cheng 4 ; Lee, Huei-Jane 2 ; Chen-Yang, Shen 5 ; Chun-Wen, Cheng 6 

 Graduate Institute of Integrated Medicine, China Medical University, Taichung 40202, Taiwan; [email protected]; Center for Personalized Medicine, China Medical University Hospital, Taichung 40202, Taiwan 
 Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan; [email protected] (J.-Y.L.); [email protected] (H.-F.Y.); [email protected] (Y.-H.H.); [email protected] (H.-J.L.) 
 Department of Biomedical Sciences, Chung Shan Medical University, Taichung 40201, Taiwan; [email protected] 
 School of Medicine, Fu Jen Catholic University, Taipei 24205, Taiwan; [email protected] 
 Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Graduate Institute of Environmental Science, China Medical University, Taichung 40202, Taiwan 
 Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan; [email protected] (J.-Y.L.); [email protected] (H.-F.Y.); [email protected] (Y.-H.H.); [email protected] (H.-J.L.); Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan 
First page
172
Publication year
2020
Publication date
2020
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2548681185
Copyright
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.