Diarylquinoline compounds induce autophagy-associated cell death by inhibiting the Akt pathway and increasing reactive oxygen species in human nasopharyngeal carcinoma cells

作者：Cai, Yuchen; Wang, Zhihui; Sun, Tiemin; Shi, Yanxia; Sun, Yueli; Huang, Peiyu; Li, Su; Jiang, Wenqi^*

来源：Oncology Reports, 2013, 29(3): 983-992.

DOI：10.3892/or.2012.2207

• diarylquinoline compounds
• anticancer
• caspase-independent
• cell death
• autophagy

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 -methylpiperazinl-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 (Delta Psi m) and ATP concentrations were decreased.

• 出版日期2013-3
• 单位沈阳药科大学; 中山大学