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

Cai,Yuchen; Wan,Zhihui; Sun,Tiemin; Shi,Yanxia; Sun,Yueli; Huang,Peiyu; Li,Su; Jiang,Wenqi

doi:10.3892/or.2012.2207

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

Authors:
- Yuchen Cai
- Zhihui Wan
- Tiemin Sun
- Yanxia Shi
- Yueli Sun
- Peiyu Huang
- Su Li
- Wenqi Jiang
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Affiliations: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China, Department of Medical Oncology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, P.R. China, Shenyang Pharmaceutical University, Shenyang, Liaoning, P.R. China
Published online on: December 24, 2012 https://doi.org/10.3892/or.2012.2207
Pages: 983-992

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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.

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