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Aurora-A kinase inhibition enhances the cytosine arabinoside-induced cell death in leukemia cells through apoptosis and mitotic catastrophe

Authors
 June-Won Cheong  ;  Haeng-Im Jung  ;  Ju In Eom  ;  Soo Jung Kim  ;  Hoi-Kyung Jeung  ;  Yoo Hong Min 
Citation
 Cancer Letters, Vol.297(2) : 171-181, 2010 
Journal Title
 Cancer Letters 
ISSN
 0304-3835 
Issue Date
2010
MeSH
Apoptosis/drug effects ; Aurora Kinases ; Caspases/metabolism ; Cell Cycle/drug effects ; Cell Death/drug effects ; Cell Line, Tumor ; Cell Survival ; Cytarabine/pharmacology* ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/enzymology ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Myeloid, Acute/therapy* ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/drug effects ; Mitochondria/genetics ; Mitochondria/metabolism ; Mitosis/drug effects ; Protein-Serine-Threonine Kinases/antagonists & inhibitors* ; Protein-Serine-Threonine Kinases/genetics ; RNA, Small Interfering/administration & dosage ; RNA, Small Interfering/genetics ; Transfection ; p38 Mitogen-Activated Protein Kinases/metabolism
Keywords
Aurora kinase ; Acute leukemia ; Ara-C ; Apoptosis ; Mitotic catastrophe
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0304383510002855
DOI
10.1016/j.canlet.2010.05.009
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Soo Jeong(김수정) ORCID logo https://orcid.org/0000-0001-8859-3573
Min, Yoo Hong(민유홍) ORCID logo https://orcid.org/0000-0001-8542-9583
Eom, Ju In(엄주인)
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
Jeung, Hoi Kyung(정회경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/101682
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