Targeting Survivin Expression Induces Cell Proliferation Defect and SubsequentCell Death Involving Mitochondrial Pathway in Myeloid Leukemic Cells

• DOI: 10.4161/cc.2.5.500
• Publication Date: 2011-01-21T19:14:57Z
• Authors: Bing Z. Carter; Rui-Yu Wang; Wendy D Schober; Michele Milella; David Chism; Michael Andreeff
• Keywords: Survivin; UVB-induced apoptosis

Survivin, a member of inhibitor apoptosis family proteins, plays important roles in both cell proliferation and death. We previously observed that Survivin is overexpressed leukemic lines blasts from patients with acute myelogenous leukemia (AML). To understand the AML search for new approaches to treatment AML, we inhibited expression HL-60 cells anti-sense oligonucleotide (sur-AS-ODN) (ISIS 23722). This blocked significant numbers G2/M phase, halted at 24 hrs progressing over time. There was only slight increase number apoptotic compared treated nonsense (NS-ODN). At 48 hrs, however, there were increases sub-G1 phase annexin V+ cells, suggesting division defects caused supported by finding reduction protein sur-AS-ODN under serum-free medium did not induce block death NS-ODN. The formation polyploid after treatment, as activation caspase 3, which suggested had occurred. mitochondrial release cytochrome C Smac nuclear translocation apoptosis-inducing factor also detected. Our results suggest essential cycle progression cells. Reduced causes cell-cycle defect leads through pathway. has potential utility therapy AML.