title: 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.affiliation: Department of Radiological Life Sciences, Graduate School of Health Sciences, Hirosaki University, Aomori, Japan.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chai
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hazawa
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Jun
authors.initials: J
authors.lastname: Igarashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suga
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
mesh_terms: D000166:Acridines / Q000494:pharmacology / Q000627:therapeutic use*; D054742:Acyl-Butyrolactones / Q000494:pharmacology / Q000627:therapeutic use*; D000873:Anthracenes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D062951:Endoreduplication / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008938:Mitosis / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000166:Acridines; D054742:Acyl-Butyrolactones; D000873:Anthracenes; D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; C432165:pyrazolanthrone; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases