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Article

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

by
Wen-Ling Liao
1,2,
Jing-Yi Lin
3,
Jia-Ching Shieh
4,
Hsiao-Fong Yeh
3,
Yi-Hsien Hsieh
3,
Yu-Chun Cheng
5,
Huei-Jane Lee
3,
Chen-Yang Shen
6,7,* and
Chun-Wen Cheng
3,8,*
1
Graduate Institute of Integrated Medicine, China Medical University, Taichung 40202, Taiwan
2
Center for Personalized Medicine, China Medical University Hospital, Taichung 40202, Taiwan
3
Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan
4
Department of Biomedical Sciences, Chung Shan Medical University, Taichung 40201, Taiwan
5
School of Medicine, Fu Jen Catholic University, Taipei 24205, Taiwan
6
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
7
Graduate Institute of Environmental Science, China Medical University, Taichung 40202, Taiwan
8
Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(1), 172; https://doi.org/10.3390/ijms21010172
Submission received: 3 November 2019 / Revised: 19 December 2019 / Accepted: 21 December 2019 / Published: 25 December 2019
(This article belongs to the Section Molecular Oncology)
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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.
Keywords: diosgenin; breast cancer; cell cycle; Chk1; apoptosis; ∆Ψm diosgenin; breast cancer; cell cycle; Chk1; apoptosis; ∆Ψm

Share and Cite

MDPI and ACS Style

Liao, W.-L.; Lin, J.-Y.; Shieh, J.-C.; Yeh, H.-F.; Hsieh, Y.-H.; Cheng, Y.-C.; Lee, H.-J.; Shen, C.-Y.; Cheng, C.-W. 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. Int. J. Mol. Sci. 2020, 21, 172. https://doi.org/10.3390/ijms21010172

AMA Style

Liao W-L, Lin J-Y, Shieh J-C, Yeh H-F, Hsieh Y-H, Cheng Y-C, Lee H-J, Shen C-Y, Cheng C-W. 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. International Journal of Molecular Sciences. 2020; 21(1):172. https://doi.org/10.3390/ijms21010172

Chicago/Turabian Style

Liao, Wen-Ling, Jing-Yi Lin, Jia-Ching Shieh, Hsiao-Fong Yeh, Yi-Hsien Hsieh, Yu-Chun Cheng, Huei-Jane Lee, Chen-Yang Shen, and Chun-Wen Cheng. 2020. "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" International Journal of Molecular Sciences 21, no. 1: 172. https://doi.org/10.3390/ijms21010172

APA Style

Liao, W.-L., Lin, J.-Y., Shieh, J.-C., Yeh, H.-F., Hsieh, Y.-H., Cheng, Y.-C., Lee, H.-J., Shen, C.-Y., & Cheng, C.-W. (2020). 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. International Journal of Molecular Sciences, 21(1), 172. https://doi.org/10.3390/ijms21010172

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