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 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.

• Authors: Xue Zhu, Ke Wang, Kai Zhang, Ting Zhang, Yongxiang Yin, Fei Xu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 17 Issue 11 (Nov 22 2016) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 27879682 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• BAX protein, human
• BCL2 protein, human
• CCNB1 protein, human
• Cyclin B1
• Cyclin-Dependent Kinase Inhibitor p21
• FAS protein, human
• Proto-Oncogene Proteins c-bcl-2
• RNA, Small Interfering
• Saponins
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• fas Receptor
• ziyuglycoside I
• CDC25C protein, human
• cdc25 Phosphatases

Topics

• Aged
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclin B1 (genetics, metabolism)
• Cyclin-Dependent Kinase Inhibitor p21 (agonists, genetics, metabolism)
• Female
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Gene Expression Regulation, Neoplastic
• Humans
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Saponins (pharmacology)
• Signal Transduction
• Tumor Suppressor Protein p53 (agonists, antagonists & inhibitors, genetics, metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)
• cdc25 Phosphatases (genetics, metabolism)
• fas Receptor (genetics, metabolism)