Source:http://linkedlifedata.com/resource/pubmed/id/20180813
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2010-6-10
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pubmed:abstractText |
Aurora A kinase plays an essential role in the proper assembly and function of the mitotic spindle. We have shown previously that Aurora A expression is increased aberrantly in human T-cell leukemia virus type 1 (HTLV-1)-infected T-cell lines and primary adult T-cell leukemia cells, and a pan-Aurora kinase inhibitor, which inhibits both Aurora A and Aurora B kinases, reduces viability and induces apoptosis in these cells. However, the specific effects of Aurora A inhibition on HTLV-1-infected T-cells are poorly understood. In this study, we addressed this question by comparing the effects of MLN8237, a selective inhibitor of Aurora A, on cell viability, cell cycle progression, and induction of apoptosis in HTLV-1-infected and -uninfected T-cell lines. MLN8237 reduced the viability of HTLV-1-infected T-cell lines within 24 h, but its effects on that of HTLV-1-uninfected T-cell lines were moderate. MLN8237 induced early apoptosis of HTLV-1-infected T-cell lines without induction of polyploidy. It induced p53 and p21 expression in HTLV-1-infected but not in -uninfected T-cell lines, suggesting that MLN8237-treated HTLV-1-infected T-cell lines exit from mitosis and activate a p53-dependent postmitotic G(1) checkpoint, leading to G(1) arrest followed by the induction of apoptosis. Our results suggest that specific inhibition of Aurora A kinase is a potentially useful therapeutic strategy in the treatment of adult T-cell leukemia and that further in vivo exploration is warranted.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Azepines,
http://linkedlifedata.com/resource/pubmed/chemical/MLN 8237,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/aurora kinase
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1349-7006
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1204-11
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pubmed:dateRevised |
2011-7-11
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pubmed:meshHeading |
pubmed-meshheading:20180813-Apoptosis,
pubmed-meshheading:20180813-Azepines,
pubmed-meshheading:20180813-Cell Line, Tumor,
pubmed-meshheading:20180813-Cell Survival,
pubmed-meshheading:20180813-Humans,
pubmed-meshheading:20180813-Leukemia-Lymphoma, Adult T-Cell,
pubmed-meshheading:20180813-Protein Kinase Inhibitors,
pubmed-meshheading:20180813-Protein-Serine-Threonine Kinases,
pubmed-meshheading:20180813-Pyrimidines,
pubmed-meshheading:20180813-T-Lymphocytes
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pubmed:year |
2010
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pubmed:articleTitle |
Aurora A selective inhibitor MLN8237 suppresses the growth and survival of HTLV-1-infected T-cells in vitro.
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pubmed:affiliation |
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. mtomita@med.u-ryukyu.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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