title: Diarylquinoline compounds induce autophagy-associated cell death by             inhibiting the Akt pathway and increasing reactive oxygen species in human nasopharyngeal             carcinoma cells.
abstract: Diarylquinoline compounds are newly synthesized derivatives of the new anti-tuberculosis             drug, TMC207. In this study, nine diarylquinoline compounds were screened for             cytotoxic activity against human tumor cells, and their mechanisms of action were             investigated. Among the nine compounds, STM-57 [N-((6-bromo-2-methoxyquinolin-3-yl)(phenyl)methl)-N-(3,4-dichlorophenyl)-3-(4             -methylpiperazin-1-yl)propanamide] showed potent cytotoxic activity. STM-57 induced             caspase-independent cell death in the human nasopharyngeal carcinoma cell line,             CNE-2. Further investigation showed that STM-57 induced autophagy, as determined             with the increased expression of green fluorescent protein-light chain 3 (GFP-LC3)             and increased LC3-II levels. STM-57 inhibited the phosphorylation of Akt and the             mammalian target of rapamycin (mTOR) in CNE-2 cells. The intracellular calcium             concentration and reactive oxygen species levels were increased in CNE-2 cells             following treatment with STM-57, whereas the mitochondrial transmembrane potential             (ΔΨm) and ATP concentrations were decreased.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, PR China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Cai
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Wan
authors.forename: Tiemin
authors.initials: T
authors.lastname: Sun
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Shi
authors.forename: Yueli
authors.initials: Y
authors.lastname: Sun
authors.forename: Peiyu
authors.initials: P
authors.lastname: Huang
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.forename: Wenqi
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D002277:Carcinoma; D045744:Cell Line, Tumor; D064687:Diarylquinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D064687:Diarylquinolines; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C587678:N-((6-bromo-2-methoxyquinolin-3-yl)(phenyl)methl)-N-(3,4-dichlorophenyl)-3-(4-methylpiperazin-1-yl)propanamide; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt