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

Bing Z. Carter, Rui Yu Wang, Wendy D. Schober, Michele Milella, David Chism, Michael Andreeff

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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 leukemic cell lines and blasts from patients with acute myelogenous leukemia (AML). To understand the roles of Survivin in AML and search for new approaches to the treatment of AML, 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 annexin V+ 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 caspase 3, which suggested that apoptotic cell death had occurred. The mitochondrial release of cytochrome C and Smac and the nuclear translocation of the apoptosis-inducing factor were also detected. Our results suggest that Survivin is essential for cell cycle progression in leukemic 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 patients with AML.

Original languageEnglish
Pages (from-to)488-493
Number of pages6
JournalCell Cycle
Volume2
Issue number5
Publication statusPublished - Sep 2003

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Cell proliferation
Cell death
Myeloid Cells
Cell Death
Acute Myeloid Leukemia
Cells
Cell Proliferation
Defects
HL-60 Cells
Cell Division
Cell Cycle
Apoptosis Inducing Factor
Inhibitor of Apoptosis Proteins
Polyploidy
Antisense Oligonucleotides
G2 Phase
Annexin A5
Serum-Free Culture Media
G1 Phase
Cytochromes

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Targeting Survivin expression induces cell proliferation defect and subsequent cell death involving mitochondrial pathway in myeloid leukemic cells. / Carter, Bing Z.; Wang, Rui Yu; Schober, Wendy D.; Milella, Michele; Chism, David; Andreeff, Michael.

In: Cell Cycle, Vol. 2, No. 5, 09.2003, p. 488-493.

Research output: Contribution to journalArticle

Carter, Bing Z. ; Wang, Rui Yu ; Schober, Wendy D. ; Milella, Michele ; Chism, David ; Andreeff, Michael. / Targeting Survivin expression induces cell proliferation defect and subsequent cell death involving mitochondrial pathway in myeloid leukemic cells. In: Cell Cycle. 2003 ; Vol. 2, No. 5. pp. 488-493.
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