Survivin, a member of inhibitor of apoptosis family of proteins, plays important roles in both cell proliferation and cell death. We previously observed that Survivin is overexpressed in @entity1778 cell lines and blasts from @entity1 with @entity3052 ( @entity3052 ). To understand the roles of Survivin in @entity3052 and search for new approaches to the treatment of @entity3052 , we inhibited Survivin expression in HL-60 cells with a Survivin anti-sense oligonucleotide (sur-AS-ODN) (ISIS 23722). This blocked significant numbers of HL-60 cells in G2/M phase, and halted cell proliferation at 24 hrs and progressing over time. There was only a slight increase in the number of apoptotic cells at 24 hrs compared with cells treated with nonsense oligonucleotide (NS-ODN). At 48 hrs, however, there were significant increases in sub-G1 phase and @entity4404 + cells, suggesting that cell division defects caused cell death. This was supported by the finding that a reduction in the Survivin protein by sur-AS-ODN in cells under serum-free medium did not induce G2/M block and cell death compared to cells treated with NS-ODN. The formation of polyploid cells was observed 48 hrs after sur-AS-ODN treatment, as was the activation of @entity522 , which suggested that apoptotic cell death had occurred. The mitochondrial release of @entity4674 and @entity17205 and the nuclear translocation of the apoptosis-inducing factor were also detected. Our results suggest that Survivin is essential for cell cycle progression in @entity1778 cells. Reduced Survivin expression causes a cell-cycle defect that leads to cell death through a mitochondrial pathway. This finding has potential utility for therapy of @entity1 with @entity3052 .

Targeting Survivin expression induces cell proliferation defect and subsequent cell death involving mitochondrial pathway in myeloid XXXX cells.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity17205 :: ('56616', 'Gene') :: ['Smac'] @entity522 :: ('836', 'Gene') :: ['caspase 3'] @entity4404 :: ('308', 'Gene') :: ['annexin V'] @entity4674 :: ('54205', 'Gene') :: ['cytochrome C'] @entity3052 :: ('MESH:D015470', 'Disease') :: ['acute myelogenous leukemia', 'AML'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukemic']
@entity1778 :: (MESH:D007938,Disease) :: ['leukemic']
