Journal
CANCER LETTERS
Volume 357, Issue 2, Pages 591-601Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.12.023
Keywords
PLK1; BI2536; Non-small cell lung cancer; Mitosis; Spindle assembly checkpoint; Mitotic catastrophe
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Funding
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [2012R1A2A2A01011164, 2011-0030072]
- National Research Foundation of Korea [2012R1A2A2A01011164] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Polo-like kinase 1 (PLK1), a critical kinase that regulates multiple steps in mitosis, is overexpressed in diverse human cancers; thus many PLK1 inhibitors have been developed as potential cancer therapeutic agents. One of these compounds, the PLK1-specific inhibitor BI2536, has been investigated as a cytotoxic drug in several cancers, including lung cancer; however, the detailed mechanism by which BI2536 induces defects in cell proliferation of non-small cell lung cancer (NSCLC) has not yet been determined. We found that 812536 treatment resulted in mitotic arrest due to improper formation of the mitotic spindles and mitotic centrosomes. The unattached kinetochores in BI2536-treated NSCLC cells activated the spindle assembly checkpoint (SAC). The prolonged activation of the SAC led to a type of apoptotic cell death referred to as mitotic catastrophe. Finally, BI2536-treated NSCLC cells show a defect in cell proliferation. Overall, these data indicate that PLK1 inhibition via mitotic disruption represents a potential approach for the treatment of NSCLC. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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