Cloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation
Abstract Esophageal squamous cell carcinoma (ESCC) is a major type of esophageal cancer. The prognosis of patients with ESCC remains poor because of the high morbidity and mortality of the disease. One strategy for drug discovery for ESCC treatment or prevention is screening FDA-approved drugs. In t...
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Series: | Cell Death Discovery |
Online Access: | https://doi.org/10.1038/s41420-021-00509-w |
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doaj-1472610cea474d73a62b1e974d12e3d52021-07-11T11:14:09ZengNature Publishing GroupCell Death Discovery2058-77162021-06-017111110.1038/s41420-021-00509-wCloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylationBo Li0Yin Yu1Yanan Jiang2Lili Zhao3Ang Li4Mingzhu Li5Baoyin Yuan6Jing Lu7Ziming Dong8Jimin Zhao9Kangdong Liu10The Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityThe Pathophysiology Department, School of Basic Medical Sciences, College of Medicine, Zhengzhou UniversityAbstract Esophageal squamous cell carcinoma (ESCC) is a major type of esophageal cancer. The prognosis of patients with ESCC remains poor because of the high morbidity and mortality of the disease. One strategy for drug discovery for ESCC treatment or prevention is screening FDA-approved drugs. In the present study, we found that the antitussive agent cloperastine can inhibit the proliferation of ESCC cells. However, the underlying mechanism was unclear. To determine the mechanism of this inhibitory effect, we performed proteomic analysis using KYSE150 cells treated with cloperastine and DMSO. The results identified several down-regulated signaling pathways included those of three key proteins (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex 1, NADH ubiquinone oxidoreductase subunit S5, and cytochrome C oxidase subunit 6B1) involved in oxidative phosphorylation. Meanwhile, we observed that oxidative phosphorylation in mitochondria was inhibited by the drug. Importantly, cloperastine suppressed ESCC growth in a xenograft mouse model in vivo. Our findings revealed that cloperastine inhibits the proliferation of ESCC in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation.https://doi.org/10.1038/s41420-021-00509-w |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bo Li Yin Yu Yanan Jiang Lili Zhao Ang Li Mingzhu Li Baoyin Yuan Jing Lu Ziming Dong Jimin Zhao Kangdong Liu |
spellingShingle |
Bo Li Yin Yu Yanan Jiang Lili Zhao Ang Li Mingzhu Li Baoyin Yuan Jing Lu Ziming Dong Jimin Zhao Kangdong Liu Cloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation Cell Death Discovery |
author_facet |
Bo Li Yin Yu Yanan Jiang Lili Zhao Ang Li Mingzhu Li Baoyin Yuan Jing Lu Ziming Dong Jimin Zhao Kangdong Liu |
author_sort |
Bo Li |
title |
Cloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation |
title_short |
Cloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation |
title_full |
Cloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation |
title_fullStr |
Cloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation |
title_full_unstemmed |
Cloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation |
title_sort |
cloperastine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation |
publisher |
Nature Publishing Group |
series |
Cell Death Discovery |
issn |
2058-7716 |
publishDate |
2021-06-01 |
description |
Abstract Esophageal squamous cell carcinoma (ESCC) is a major type of esophageal cancer. The prognosis of patients with ESCC remains poor because of the high morbidity and mortality of the disease. One strategy for drug discovery for ESCC treatment or prevention is screening FDA-approved drugs. In the present study, we found that the antitussive agent cloperastine can inhibit the proliferation of ESCC cells. However, the underlying mechanism was unclear. To determine the mechanism of this inhibitory effect, we performed proteomic analysis using KYSE150 cells treated with cloperastine and DMSO. The results identified several down-regulated signaling pathways included those of three key proteins (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex 1, NADH ubiquinone oxidoreductase subunit S5, and cytochrome C oxidase subunit 6B1) involved in oxidative phosphorylation. Meanwhile, we observed that oxidative phosphorylation in mitochondria was inhibited by the drug. Importantly, cloperastine suppressed ESCC growth in a xenograft mouse model in vivo. Our findings revealed that cloperastine inhibits the proliferation of ESCC in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation. |
url |
https://doi.org/10.1038/s41420-021-00509-w |
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