Autor: |
Akihiro Ohashi, Momoko Ohori, Kenichi Iwai, Tadahiro Nambu, Maki Miyamoto, Tomohiro Kawamoto, Masanori Okaniwa |
Jazyk: |
angličtina |
Rok vydání: |
2015 |
Předmět: |
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Zdroj: |
PLoS ONE, Vol 10, Iss 12, p e0144675 (2015) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0144675 |
Popis: |
Centromere-associated protein E (CENP-E) regulates both chromosome congression and the spindle assembly checkpoint (SAC) during mitosis. The loss of CENP-E function causes chromosome misalignment, leading to SAC activation and apoptosis during prolonged mitotic arrest. Here, we describe the biological and antiproliferative activities of a novel small-molecule inhibitor of CENP-E, Compound-A (Cmpd-A). Cmpd-A inhibits the ATPase activity of the CENP-E motor domain, acting as a time-dependent inhibitor with an ATP-competitive-like behavior. Cmpd-A causes chromosome misalignment on the metaphase plate, leading to prolonged mitotic arrest. Treatment with Cmpd-A induces antiproliferation in multiple cancer cell lines. Furthermore, Cmpd-A exhibits antitumor activity in a nude mouse xenograft model, and this antitumor activity is accompanied by the elevation of phosphohistone H3 levels in tumors. These findings demonstrate the potency of the CENP-E inhibitor Cmpd-A and its potential as an anticancer therapeutic agent. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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