Recent evidence indicates that CXCR2 signaling is crucial for cancer 
progression, and its antagonist SB225002 induces apoptosis in Wilms' tumor 
cells. Here, we investigated the effect of SB225002 on cell cycle progression 
and apoptosis induction in vitro, using CDDP-sensitive and -resistant OVCA cell 
lines with different p53 status (wild type, mutant or null). Adenovirus 
infection of wild-type p53 or transfection of p53 siRNA was used to over-express 
or knock-down p53. Cell cycle and apoptosis were determined by flow cytometry or 
Hoechst staining and observation of nuclear morphology. Our data demonstrated 
that SB225002 induced apoptosis in both wild-type and p53-deficient ovarian 
cancer (OVCA) cells through alternative mechanisms. SB225002 promoted mitotic 
catastrophe, as evidenced by the accumulation of mitotic cells with spindle 
abnormalities, chromosome mis-segregation, multi-polar cell division, multiple 
nuclei, aneuploidy/polyploidy and subsequent extensive apoptosis. 
SB225002-induced mitotic catastrophe appeared to be mediated by down-regulation 
of checkpoint kinase Chk1 and Cdk1-cyclin B activation. In cells expressing 
wild-type p53 (OV2008 and C13*), SB225002 increased total and phospho-Ser p53 
levels, and p53 knock-down decreased SB225002-induced apoptosis, without 
affecting premature mitosis. These results suggest that SB225002 induces 
p53-dependent apoptosis, and provokes mitotic catastrophe in p53-independent 
manner in p53 wild-type cells. Reconstitution with wild-type P53 in P53-null 
SKOV3 cell attenuated SB225002-induced mitotic catastrophe, suggesting p53 
prevented mitotic catastrophe induced by SB225002 in p53-deficient OVCA cells. 
Finally, the effect of SB225002 could not be prevented by pretreatment with 
CXCR2 ligand or its neutralizing antibody. The present studies demonstrate for 
the first time that SB225002 has dual actions in OVCA cells, inducing classic 
apoptosis through p53 activation and provoking mitotic catastrophe in both p53 
wild-type and deficient cells by Chk1 inhibition and Cdk activation. These 
findings raise the possibility of SB225002 as a new candidate molecule for OVCA 
therapy independent of the p53 status.