The role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells.
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.
Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China.
Hui
H
Wang
Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China.
Changqing
C
Lu
Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China.
Qing
Q
Li
Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China.
Jun
J
Xie
Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China.
Tongbing
T
Chen
Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China.
Yan
Y
Tan
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China.
Changping
C
Wu
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China.
Jingting
J
Jiang
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D001549:Benzamides / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D061986:MCF-7 Cells; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; D004317:Doxorubicin; C025160:3-aminobenzamide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C484228:KIF4A protein, human; D016547:Kinesins
Kif4A; MCF-7; MDA-MB-231; PARP-1; doxorubicin