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...

Full description

Bibliographic Details
Main Authors: Bo Li, Yin Yu, Yanan Jiang, Lili Zhao, Ang Li, Mingzhu Li, Baoyin Yuan, Jing Lu, Ziming Dong, Jimin Zhao, Kangdong Liu
Format: Article
Language:English
Published: Nature Publishing Group 2021-06-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-021-00509-w
id doaj-1472610cea474d73a62b1e974d12e3d5
record_format Article
spelling 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
work_keys_str_mv AT boli cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT yinyu cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT yananjiang cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT lilizhao cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT angli cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT mingzhuli cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT baoyinyuan cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT jinglu cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT zimingdong cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT jiminzhao cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
AT kangdongliu cloperastineinhibitsesophagealsquamouscellcarcinomaproliferationinvivoandinvitrobysuppressingmitochondrialoxidativephosphorylation
_version_ 1721309198677966848