Frontiers in Pharmacology (Sep 2020)
Proteomics Reveal the Inhibitory Mechanism of Levodopa Against Esophageal Squamous Cell Carcinoma
- Zhenzhen Li,
- Zhenzhen Li,
- Xin Li,
- Xinyu He,
- Xinyu He,
- Xuechao Jia,
- Xuechao Jia,
- Xiaofan Zhang,
- Xiaofan Zhang,
- Bingbing Lu,
- Bingbing Lu,
- Jimin Zhao,
- Jimin Zhao,
- Jimin Zhao,
- Jing Lu,
- Jing Lu,
- Jing Lu,
- Lexia Chen,
- Lexia Chen,
- Ziming Dong,
- Ziming Dong,
- Ziming Dong,
- Ziming Dong,
- Kangdong Liu,
- Kangdong Liu,
- Kangdong Liu,
- Kangdong Liu,
- Kangdong Liu,
- Zigang Dong,
- Zigang Dong,
- Zigang Dong,
- Zigang Dong
Affiliations
- Zhenzhen Li
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Zhenzhen Li
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Xin Li
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Xinyu He
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Xinyu He
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Xuechao Jia
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Xuechao Jia
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Xiaofan Zhang
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Xiaofan Zhang
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Bingbing Lu
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Bingbing Lu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Jimin Zhao
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Jimin Zhao
- Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, China
- Jimin Zhao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Jing Lu
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Jing Lu
- Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, China
- Jing Lu
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Lexia Chen
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Lexia Chen
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Ziming Dong
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Ziming Dong
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Ziming Dong
- Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, China
- Ziming Dong
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Kangdong Liu
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Kangdong Liu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Kangdong Liu
- Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, China
- Kangdong Liu
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Kangdong Liu
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, China
- Zigang Dong
- Department of Pathophysiology, School of Basic Medical Sciences, AMS, College of Medicine, Zhengzhou University, Zhengzhou, China
- Zigang Dong
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Zigang Dong
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Zigang Dong
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, China
- DOI
- https://doi.org/10.3389/fphar.2020.568459
- Journal volume & issue
-
Vol. 11
Abstract
High recurrence rates and poor survival of patients with esophageal squamous cell carcinoma (ESCC) after treatment make ongoing research on chemoprevention drugs for ESCC particularly important. In this study, we screened a large number of FDA-approved drugs and found levodopa, a drug used to treat Parkinson’s disease, had an inhibitory effect on the growth of ESCC cells. To elucidate the molecular mechanisms involved, we applied quantitative proteomics to investigate the anti-tumor activity of levodopa on ESCC. The results suggest that levodopa could down-regulate oxidative phosphorylation, non-alcoholic fatty liver disease, and Parkinson’s disease pathways. Major mitochondrial respiratory compounds were involved in the pathways, including succinate dehydrogenase subunit D, NADH-ubiquinone oxidoreductase Fe-S protein 4, and mitochondrial cytochrome c oxidase subunit 3. Down-regulation of these proteins was associated with mitochondrial dysfunction. Western blotting and immunofluorescence results confirmed the proteomics findings. Cell viability assays indicated mitochondrial activity was suppressed after levodopa treatment. Reduced mitochondrial membrane potential was detected using JC-1 staining and TMRE assays. Transmission electron microscopy revealed changes in the morphology of mitochondria. Taken together, these results indicate that levodopa inhibited the growth of ESCC through restraining mitochondria function.
Keywords
- esophageal squamous cell carcinoma
- levodopa
- proteomic
- mitochondria
- succinate dehydrogenase subunit D
