Abstract
Aurora-A (Aur-A) is a centrosome-associated serine/threonine kinase that is overexpressed in various cancers and potentially correlated with chemoresistance. In the Ara-C-sensitive leukemia cell lines, silencing of Aur-A by small interfering RNA transfection led to a significant increase in the Ara-C-induced cell death rate through induction of mitochondria-mediated, caspase-dependent apoptosis. In contrast, combined treatment of the Ara-C-resistant leukemia cell lines with Aur-A siRNA and Ara-C remarkably enhanced the cell death rate via non-caspase-dependent mitotic catastrophe. Taken together, Aur-A inhibition was an effective treatment for both the Ara-C-sensitive and resistant leukemia cells by increasing apoptosis and mitotic catastrophe, respectively.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Aurora Kinases
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Caspases / metabolism
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Cell Cycle / drug effects
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Cell Death / drug effects
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Cell Line, Tumor
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Cell Survival
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Cytarabine / pharmacology*
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HL-60 Cells
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Humans
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Leukemia, Myeloid, Acute / drug therapy
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Leukemia, Myeloid, Acute / enzymology
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Leukemia, Myeloid, Acute / pathology
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Leukemia, Myeloid, Acute / therapy*
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Membrane Potential, Mitochondrial / drug effects
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Mitochondria / drug effects
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Mitochondria / genetics
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Mitochondria / metabolism
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Mitosis / drug effects
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / genetics
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RNA, Small Interfering / administration & dosage
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RNA, Small Interfering / genetics
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Transfection
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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RNA, Small Interfering
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Cytarabine
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Aurora Kinases
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Protein Serine-Threonine Kinases
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p38 Mitogen-Activated Protein Kinases
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Caspases