Mefloquine Inhibits Esophageal Squamous Cell Carcinoma Tumor Growth by Inducing Mitochondrial Autophagy

Yifei Xie, Jing Zhang, Bingbing Lu, Zhuo Bao, Jimin Zhao, Xianyu Lu, Yaxing Wei, Ke Yao, Yanan Jiang, Qiang Yuan, Xiaofan Zhang, Bo Li, Xinhuan Chen, Zigang Dong, Kangdong Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Esophageal squamous cell carcinoma (ESCC) has a worldwide impact on human health, due to its high incidence and mortality. Therefore, identifying compounds to increase patients' survival rate is urgently needed. Mefloquine (MQ) is an FDA-approved anti-malarial drug, which has been reported to inhibit cellular proliferation in several cancers. However, the anti-tumor activities of the drug have not yet been completely defined. In this study, mass spectrometry was employed to profile proteome changes in ESCC cells after MQ treatment. Sub-cellular localization and gene ontology term enrichment analysis suggested that MQ treatment mainly affect mitochondria. The KEGG pathway enrichment map of down-regulated pathways and Venn diagram indicated that all of the top five down regulated signaling pathways contain four key mitochondrial proteins (succinate dehydrogenase complex subunit C (SDHC), succinate dehydrogenase complex subunit D, mitochondrially encoded cytochrome c oxidase III and NADH: ubiquinone oxidoreductase subunit V3). Meanwhile, mitochondrial autophagy was observed in MQ-treated KYSE150 cells. More importantly, patient-derived xenograft mouse models of ESCC with SDHC high expression were more sensitive to MQ treatment than low SDHC-expressing xenografts. Taken together, mefloquine inhibits ESCC tumor growth by inducing mitochondrial autophagy and SDHC plays a vital role in MQ-induced anti-tumor effect on ESCC.

Original languageEnglish (US)
Article number1217
JournalFrontiers in Oncology
Volume10
DOIs
StatePublished - Jul 28 2020

Bibliographical note

Funding Information:
This research was funded by the National Natural Science Foundations of China (grant number 81872335), National Natural Science Youth Foundation (grant number 81902486), National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China (No. 2018ZX09711002), the Natural Science Foundation of Henan (grant number 161100510300), and China Scholarship Council.

Keywords

  • autophagy
  • esophageal squamous cell carcinoma (ESCC)
  • mefloquine (MQ)
  • mitochondria
  • succinate dehydrogenase complex subunit C (SDHC)

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