title: 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.
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 herbalRadix 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. zhuxue@jsinm.org.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. wangke@jsinm.org.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. zhangkai@jsinm.org.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: The Affiliated Maternity and Children Health Hospital of Nanjing Medical University, Wuxi 214002, China. zhangting040715@163.com.|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. zhangting040715@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pathology, the Affiliated Maternity and Children Health Hospital of Nanjing Medical University, Wuxi 214002, China. yinyongxiang0118@outlook.com.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Laboratory Medicine, the Affiliated Maternity and Children Health Hospital of Nanjing Medical University, Wuxi 214002, China. xfxnn@outlook.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
mesh_terms: D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000595707:BCL2 protein, human; C534699:CCNB1 protein, human; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; C491901:FAS protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D012503:Saponins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C484848:ziyuglycoside I; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases
keywords: G2/M phase arrest; MDA-MB-231 cell line; intrinsic and extrinsic apoptosis; ziyuglycoside I