Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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The Role of Kif4A in Doxorubicin-Induced Apoptosis in Breast Cancer Cells

  • Wang, Hui (Department of Pathology, The Third Affiliated Hospital of Soochow University) ;
  • Lu, Changqing (Department of Pathology, The Third Affiliated Hospital of Soochow University) ;
  • Li, Qing (Department of Pathology, The Third Affiliated Hospital of Soochow University) ;
  • Xie, Jun (Department of Pathology, The Third Affiliated Hospital of Soochow University) ;
  • Chen, Tongbing (Department of Pathology, The Third Affiliated Hospital of Soochow University) ;
  • Tan, Yan (Department of Pathology, The Third Affiliated Hospital of Soochow University) ;
  • Wu, Changping (Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University) ;
  • Jiang, Jingting (Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University)
  • Received : 2014.07.28
  • Accepted : 2014.09.05
  • Published : 2014.11.30
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Abstract

This study was to investigate the mechanism and role of Kif4A in doxorubicin-induced apoptosis in breast cancer. Using two human breast cancer cell lines MCF-7 (with wild-type p53) and MDA-MB-231 (with mutant p53), we quantitated the expression levels of kinesin super-family protein 4A (Kif4A) and poly (ADP-ribose) Polymerase-1 (PARP-1) by Western blot after doxorubicin treatment and examined the apoptosis by flow cytometry after treatment with doxorubicin and PARP-1 inhibitor, 3-Aminobenzamide (3-ABA). Our results showed that doxorubicin treatment could induce the apoptosis of MCF-7 and MDA-MB-231 cells, the down-regulation of Kif4A and upregulation of poly(ADP-ribose) (PAR). The activity of PARP-1 or PARP-1 activation was significantly elevated by doxorubicin treatment in dose- and time-dependent manners (P < 0.05), while doxorubicin treatment only slightly elevated the level of cleaved fragments of PARP-1 (P > 0.05). We further demonstrated that overexpression of Kif4A could reduce the level of PAR and significantly increase apoptosis. The effect of doxorubicin on apoptosis was more profound in MCF-7 cells compared with MDA-MB-231 cells (P < 0.05). Taken together, our results suggest that the novel role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells is achieved by inhibiting the activity of PARP-1.

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References

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