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

  • Front Oncol. 2020 Jul 28;10:1217. doi: 10.3389/fonc.2020.01217.
Yifei Xie  1 ,  Jing Zhang  1 ,  Bingbing Lu  1 ,  Zhuo Bao  1 ,  Jimin Zhao  1  2 ,  Xianyu Lu  1 ,  Yaxing Wei  1 ,  Ke Yao  3 ,  Yanan Jiang  1 ,  Qiang Yuan  1 ,  Xiaofan Zhang  1 ,  Bo Li  1 ,  Xinhuan Chen  1  2 ,  Zigang Dong  1  3  4  5 ,  Kangdong Liu  1  2  3  4  5
Affiliations
  • 1. Department of Pathophysiology, School of Basic Medical Sciences, AMS, Zhengzhou University, Zhengzhou, China.
  • 2. Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, China.
  • 3. China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
  • 4. State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China.
  • 5. Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, China.
PMID: 32850358 DOI: 10.3389/fonc.2020.01217
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.

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