title: Survivin overexpression correlates with an apoptosis-resistant phenotype in chronic myeloid leukemia cells.
abstract: 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: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors: Gabriela
authors: G
authors: Nestal de Moraes
authors: Karina Lani
authors: KL
authors: Silva
authors: Flavia da Cunha
authors: FC
authors: Vasconcelos
authors: Raquel Ciuvalschi
authors: RC
authors: Maia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D000077022:Survivin; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D015255:Idarubicin