+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Cell Cycle 2(5): 488-493



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.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 050500631

Download citation: RISBibTeXText

PMID: 12963850


Related references

Targeting Survivin Expression Induces Cell Proliferation Defect and SubsequentCell Death Involving Mitochondrial Pathway in Myeloid Leukemic Cells. Cell Cycle 2(5): 486-491, 2003

Targeting Survivin Expression Induces G2/M Block and Subsequent Cell Death in Myeloid Leukemic Cells. Blood 100(11): Abstract No 4612, 2002

Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells. Blood 108(2): 630-637, 2006

The small-molecule compound AC-73 targeting CD147 inhibits leukemic cell proliferation, induces autophagy and increases the chemotherapeutic sensitivity of acute myeloid leukemia cells. Haematologica 104(5): 973-985, 2019

Euphorbia formosana root extract induces apoptosis by caspase-dependent cell death via Fas and mitochondrial pathway in THP-1 human leukemic cells. Molecules 18(2): 1949-1962, 2013

STI571 induces another cell death pathway, necrosis-like programmed cell death, in BCR-ABL positive human leukemic cells. Proceedings of the American Association for Cancer Research Annual Meeting 44: 611-612, 2003

Arsenic trioxide induces apoptosis in B-cell chronic lymphocytic leukemic cells through down-regulation of survivin via the p53-dependent signaling pathway. Leukemia Research 37(12): 1719-1725, 2013

HIF-1α inhibition by 2-methoxyestradiol induces cell death via activation of the mitochondrial apoptotic pathway in acute myeloid leukemia. Cancer Biology and Therapy 17(6): 625-634, 2016

Sorafenib induces apoptotic cell death in human non-small cell lung cancer cells by down-regulating mammalian target of rapamycin (mTOR)-dependent survivin expression. Biochemical Pharmacology 82(3): 216-226, 2011

FLI-06 suppresses proliferation, induces apoptosis and cell cycle arrest by targeting LSD1 and Notch pathway in esophageal squamous cell carcinoma cells. Biomedicine and PharmacoTherapy 107: 1370-1376, 2018

Delta-lactoferrin induces cell death via the mitochondrial death signaling pathway by upregulating bax expression. Biometals 27(5): 875-889, 2014

Curcumin induces small cell lung cancer NCI-H446 cell apoptosis via the reactive oxygen species-mediated mitochondrial pathway and not the cell death receptor pathway. Dna and Cell Biology 31(2): 139-150, 2012

CD44 ligation inhibits the proliferation of acute myeloid leukemic cells and induces the accumulation of the cell cycle inhibitor p27kip1. Experimental Hematology 29(8 Suppl. 1): 104, 2001

14-Deoxy-11,12-didehydroandrographolide inhibits proliferation and induces GSH-dependent cell death of human promonocytic leukemic cells. Journal of Natural Medicines 68(2): 387-394, 2014

Doxorubicin induces cell death in breast cancer cells regardless of Survivin and XIAP expression levels. European Journal of Cell Biology 92(8-9): 247-256, 2014