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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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Article

The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo

  • Authors:
    • Gui'e Xie
    • Hongping Tang
    • Shaoqing Wu
    • Jingsong Chen
    • Jiangwen Liu
    • Can Liao
  • View Affiliations / Copyright

    Affiliations: Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, P.R. China, Department of Pathology, Shenzhen Maternity and Child Healthcare Hospital Affiliated to Southern Medical University, Shenzhen 518028, P.R. China, College of Light Industry and Food Science, South China University of Technology, Guangzhou 510640, P.R. China
  • Pages: 804-812
    |
    Published online on: May 26, 2014
       https://doi.org/10.3892/ijo.2014.2467
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Abstract

Inhibitors of cyclin-dependent kinases (Cdks) have been reported to have activities in many types of cancer cells by inhibiting Cdk7 and Cdk9, which control transcription. SNS-032 is a potent and selective inhibitor of Cdk2, Cdk7 and Cdk9 and has emerged in clinical trials. Here, we examined the viability of MCF-7 and MDA-MB-435 breast cancer cells in the presence of SNS-032 and observed a dose-dependent inhibition of cellular proliferation in both cell lines. SNS-032 had a direct apoptosis-inducing effect through both the extrinsic and intrinsic apoptotic pathways in breast cancer cells as shown by a dose-dependent increase in Annexin V-positive cells and terminal deoxynucleotidyl transferase-mediated dUTP nick?end labeling (TUNEL)-positive cells, as well as activation of caspase-8, -9 and poly(ADP-ribose) polymerase (PARP). At the molecular level, SNS-032 induced a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and blocked RNA synthesis. Consistent with the inherently rapid turnover rates of their transcripts and proteins, the anti-apoptotic proteins Mcl-1 and X-linked inhibitor of apoptosis protein (XIAP) were rapidly reduced on exposure to SNS-032. Our results also indicated that SNS-032 suppressed the growth of breast cancer xenografts in mice. These data demonstrate that the use of SNS-032 may be a rational and novel therapeutic strategy for human breast cancer and warrants further clinical investigation.
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Copy and paste a formatted citation
Spandidos Publications style
Xie G, Tang H, Wu S, Chen J, Liu J and Liao C: The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo. Int J Oncol 45: 804-812, 2014.
APA
Xie, G., Tang, H., Wu, S., Chen, J., Liu, J., & Liao, C. (2014). The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo. International Journal of Oncology, 45, 804-812. https://doi.org/10.3892/ijo.2014.2467
MLA
Xie, G., Tang, H., Wu, S., Chen, J., Liu, J., Liao, C."The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo". International Journal of Oncology 45.2 (2014): 804-812.
Chicago
Xie, G., Tang, H., Wu, S., Chen, J., Liu, J., Liao, C."The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo". International Journal of Oncology 45, no. 2 (2014): 804-812. https://doi.org/10.3892/ijo.2014.2467
Copy and paste a formatted citation
x
Spandidos Publications style
Xie G, Tang H, Wu S, Chen J, Liu J and Liao C: The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo. Int J Oncol 45: 804-812, 2014.
APA
Xie, G., Tang, H., Wu, S., Chen, J., Liu, J., & Liao, C. (2014). The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo. International Journal of Oncology, 45, 804-812. https://doi.org/10.3892/ijo.2014.2467
MLA
Xie, G., Tang, H., Wu, S., Chen, J., Liu, J., Liao, C."The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo". International Journal of Oncology 45.2 (2014): 804-812.
Chicago
Xie, G., Tang, H., Wu, S., Chen, J., Liu, J., Liao, C."The cyclin-dependent kinase inhibitor SNS-032 induces apoptosis in breast cancer cells via depletion of Mcl-1 and X-linked inhibitor of apoptosis protein and displays antitumor activity in vivo". International Journal of Oncology 45, no. 2 (2014): 804-812. https://doi.org/10.3892/ijo.2014.2467
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