Polo-like kinase 1 inhibitor BI2536 causes mitotic catastrophe following activation of the spindle assembly checkpoint in non-small cell lung cancer cells. Issue 2 (28th February 2015)

• Record Type: Journal Article
• Authors: Choi, Minji; Kim, Wootae; Cheon, Min Gyeong; Lee, Chang-Woo; Kim, Ja-Eun
• Is Part Of: Cancer letters. Volume 357:Issue 2(2015)
• Page Start: 591
• Page End: 601
• Publication Date: 2015-02-28
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2014.12.023
• Languages: English
• ISSNs: 0304-3835

Abstract

<abstract abstract-type="author" id="ab0010"> <title id="st0010">Abstract</title> <sec> <p id="sp0010">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 BI2536 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.</p> </sec> </abstract>