Novel acridine-based N-acyl-homoserine lactone analogs induce endoreduplication in the human oral squamous carcinoma cell line SAS.

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.
Authors	Hongbo Chai, Masaharu Hazawa, Yoichiro Hosokawa, Jun Igarashi, Hiroaki Suga, Ikuo Kashiwakura
Journal	Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 35 Issue 8 Pg. 1257-63 ( 2012) ISSN: 1347-5215 [Electronic] Japan
PMID	22863922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Acridines Acyl-Butyrolactones Anthracenes Antineoplastic Agents Radiation-Sensitizing Agents pyrazolanthrone Protein Serine-Threonine Kinases JNK Mitogen-Activated Protein Kinases
Topics	Acridines (pharmacology, therapeutic use) Acyl-Butyrolactones (pharmacology, therapeutic use) Anthracenes (pharmacology) Antineoplastic Agents (pharmacology, therapeutic use) Carcinoma, Squamous Cell (drug therapy, metabolism, radiotherapy) Cell Cycle Checkpoints (drug effects) Cell Death (drug effects) Cell Line, Tumor Cell Survival (drug effects) Endoreduplication (drug effects) Humans JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors) Mitosis (drug effects) Mouth Neoplasms (drug therapy, metabolism, radiotherapy) Polyploidy Protein Serine-Threonine Kinases (metabolism) Radiation-Sensitizing Agents (pharmacology, therapeutic use)

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