Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Novel Acridine-Based N-Acyl-homoserine Lactone Analogs Induce Endoreduplication in the Human Oral Squamous Carcinoma Cell Line SAS
Hongbo ChaiMasaharu HazawaYoichiro HosokawaJun IgarashiHiroaki SugaIkuo Kashiwakura
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2012 Volume 35 Issue 8 Pages 1257-1263

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Abstract

The cytotoxicity of novel acridine-based N-acyl-homoserine lactone (AHL) analogs was investigated on the human oral squamous carcinoma cell line SAS. One analog induced G2/M phase arrest at 5.3–10.6 µM and induced polyploidy at a higher dose (21.2 µM). Importantly, treatment of SAS cells with a combination of the AHL analog and the Jun N-terminal kinase (JNK) inhibitor, SP600125, prevented mitosis and induced polyploidy. The AHL analog synergized with X-irradiation to inhibit clonogenic survival of SAS cells; however, its radiosensitizing effects were relative to not X-irradiation-induced apoptosis but mitotic failure following enhanced expression of Aurora A and B. These results suggest that the active AHL analog showed growth-suppressive and radiosensitizing effects, which involve polyploidy followed by G2/M accumulation and atypical cell death in the SAS cell line.

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© 2012 The Pharmaceutical Society of Japan
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