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Int. J. Mol. Sci. 2016, 17(11), 1903; doi:10.3390/ijms17111903

Ziyuglycoside I Inhibits the Proliferation of MDA-MB-231 Breast Carcinoma Cells through Inducing p53-Mediated G2/M Cell Cycle Arrest and Intrinsic/Extrinsic Apoptosis

1,†
,
1,†
,
1
,
2,3
,
4
and
5,*
1
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China
2
The Affiliated Maternity and Children Health Hospital of Nanjing Medical University, Wuxi 214002, China
3
Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment Cancer Center, School of Public Health, Nanjing Medical University, Nanjing 210029, China
4
Department of Pathology, the Affiliated Maternity and Children Health Hospital of Nanjing Medical University, Wuxi 214002, China
5
Department of Laboratory Medicine, the Affiliated Maternity and Children Health Hospital of Nanjing Medical University, Wuxi 214002, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Masato Matsuoka
Received: 12 August 2016 / Revised: 6 November 2016 / Accepted: 10 November 2016 / Published: 22 November 2016
(This article belongs to the Section Molecular Toxicology)
View Full-Text   |   Download PDF [3616 KB, uploaded 22 November 2016]   |  

Abstract

Background: Due to the aggressive clinical behavior, poor outcome, and lack of effective specific targeted therapies, triple-negative breast cancer (TNBC) has currently been recognized as one of the most malignant types of tumors. In the present study, we investigated the cytotoxic effect of ziyuglycoside I, one of the major components extracted from Chinese anti-tumor herbal Radix Sanguisorbae, on the TNBC cell line MDA-MB-231. Methods: The underlying molecular mechanism of the cytotoxic effect ziyuglycoside I on MDA-MB-231 cells was investigated with cell viability assay, flow cytometric analysis and Western blot. Results: Compared to normal mammary gland Hs 578Bst cells, treatment of ziyuglycoside I resulted in a significant growth inhibitory effect on MDA-MB-231 cells. Ziyuglycoside I induced the G2/M phase arrest and apoptosis of MDA-MB-231 cells in a dose-dependent manner. These effects were found to be partially mediated through the up-regulation of p53 and p21WAF1, elevated Bax/Bcl-2 ratio, and the activation of both intrinsic (mitochondrial-initiated) and extrinsic (Fas/FasL-initiated) apoptotic pathways. Furthermore, the p53 specific siRNA attenuated these effects. Conclusion: Our study suggested that ziyuglycoside I-triggered MDA-MB-231 cell cycle arrest and apoptosis were probably mediated by p53. This suggests that ziyuglycoside I might be a potential drug candidate for treating TNBC. View Full-Text
Keywords: ziyuglycoside I; MDA-MB-231 cell line; G2/M phase arrest; intrinsic and extrinsic apoptosis ziyuglycoside I; MDA-MB-231 cell line; G2/M phase arrest; intrinsic and extrinsic apoptosis
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MDPI and ACS Style

Zhu, X.; Wang, K.; Zhang, K.; Zhang, T.; Yin, Y.; Xu, F. Ziyuglycoside I Inhibits the Proliferation of MDA-MB-231 Breast Carcinoma Cells through Inducing p53-Mediated G2/M Cell Cycle Arrest and Intrinsic/Extrinsic Apoptosis. Int. J. Mol. Sci. 2016, 17, 1903.

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