Document Detail


Survivin overexpression correlates with an apoptosis-resistant phenotype in chronic myeloid leukemia cells.
MedLine Citation:
PMID:  21431279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Survivin is a member of the inhibitor of apoptosis protein family (IAP) that acts in both inhibition of apoptosis and regulation of the cell cycle. Despite the fact that survivin is overexpressed in almost all human malignancies, its expression is undetectable in most normal adult tissues, which is what makes it a potential target for anticancer interventions. The aim of this work was to investigate whether survivin is involved in resistance to idarubicin (ida), a drug commonly used in leukemia treatment. Cytotoxic assays using MTT showed that 1 µM of ida could inhibit 50% of cell viability in K562, a chronic myeloid leukemia cell line. Western blotting analysis revealed that survivin expression was increased in the cell line after treatment with ida 0.5 and 1 µM concentrations, protecting cells from ida-induced apoptosis. However, the highest ida concentrations tested were able to inhibit survivin levels and induce apoptosis in K562 cells, as evaluated by morphology and caspase-3 and -9 activation. These results indicate that survivin expression is involved in ida resistance in K562 leukemic cells. Flow cytometry analysis of the cell cycle showed that ida induced G2/M arrest in these cells and there was a statistically significant positive correlation between survivin expression and the percentage of cells in G2/M phase. This work supports the idea that survivin may contribute to an apoptosis-resistant phenotype by inhibiting ida-induced apoptosis and preventing cells from progressing in the cell cycle.
Authors:
Gabriela Nestal de Moraes; Karina Lani Silva; Flavia da Cunha Vasconcelos; Raquel Ciuvalschi Maia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-22
Journal Detail:
Title:  Oncology reports     Volume:  25     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-04-19     Completed Date:  2011-08-08     Revised Date:  2011-08-19    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1613-9     Citation Subset:  IM    
Affiliation:
Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology
Apoptosis / genetics*
Blotting, Western
Cell Cycle / drug effects
Cell Line, Tumor
Drug Resistance, Neoplasm / genetics*
Humans
Idarubicin / pharmacology
Inhibitor of Apoptosis Proteins / biosynthesis*,  genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*,  metabolism
Phenotype
Up-Regulation
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/BIRC5 protein, human; 0/Inhibitor of Apoptosis Proteins; 58957-92-9/Idarubicin

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