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http://dx.doi.org/10.14348/molcells.2014.0210

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)
Publication Information
Molecules and Cells / v.37, no.11, 2014 , pp. 812-818 More about this Journal
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.
Keywords
doxorubicin; Kif4A; MCF-7; MDA-MB-231; PARP-1;
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