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

doi:10.3390/ijms21010172

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 310902500/24709

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24709

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
Authors:	Liao, WL;Lin, JY;Shieh, JC;Yeh, HF;Hsieh, YH;Cheng, YC;Lee, HJ;Shen, CY;Cheng, CW
Keywords:	diosgenin;breast cancer;cell cycle;Chk1;apoptosis;Psi m
Date:	2020
Issue Date:	2022-08-09T08:06:44Z (UTC)
Publisher:	MDPI
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-Chk1(Ser345)) and cyclin B expression, which resulted in G2/M phase blockade. Mechanistically, Cdc25C-Cdc2 signaling was involved in inactivating Chk1(Ser345) 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.
URI:	http://dx.doi.org/10.3390/ijms21010172 https://www.webofscience.com/wos/woscc/full-record/WOS:000515378000172 https://ir.csmu.edu.tw:8080/handle/310902500/24709
Relation:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ,2020 ,v21 ,issue 1
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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