Inhibition of mitochondria NADH-Ubiquinone oxidoreductase (complex I) sensitizes the radioresistant glioma U87MG cells to radiation.

Brain Neoplasms / enzymology Cell Line, Tumor Electron Transport Complex I / antagonists & inhibitors Enzyme Inhibitors / pharmacology Glioma / enzymology Humans Metformin / pharmacology Mitochondria / drug effects Radiation Tolerance / drug effects Radiation-Sensitizing Agents / pharmacology Rotenone / pharmacology
Complex I Glioma Metformin Mitochondria metabolism Radioresistance Rotenone

Journal

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295

Informations de publication

Date de publication:
Sep 2020
Historique:
received: 06 12 2019
revised: 19 06 2020
accepted: 24 06 2020
pubmed: 10 8 2020
medline: 27 2 2021
entrez: 10 8 2020
Statut: ppublish

Résumé

Radiation is a current standard treatment of glioma. The fractionated radiotherapy with low dose of radiation over weeks has been employed in glioma patients, while radiotherapy can only offer palliation due to the radioresistance. We cumulatively radiated a glioblastoma cell line, U87MG, and screened radioresistant glioma cells. A transcriptome sequencing was performed to analyze the transcription differences between the raidoresistant and control cells, which showed the mitochondria NADH-ubiquinone oxidoreductase (Complex I) subunits were up-regulated in the radioresistant cells. The copy numbers of mitochondria were increased in the radioresistant glioma cells. After using mitochondria Complex I inhibitors, rotenone and metformin, to treat glioma cells, we found the resistant glioma cells re-sensitized to radiation. These results demonstrate that Complex I is associated with the fractioned radiation-induced radioresistance of glioma and would be a potent target for clinical radiotherapy of glioma.

Identifiants

DOI: 10.1016/j.biopha.2020.110460 PMID: 32768950
pubmed: 32768950
pii: S0753-3322(20)30653-3
doi: 10.1016/j.biopha.2020.110460
pii:
doi:

Substances chimiques

Enzyme Inhibitors 0
Radiation-Sensitizing Agents 0
Rotenone 03L9OT429T
Metformin 9100L32L2N
Electron Transport Complex I EC 7.1.1.2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

110460

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Auteurs

Xingjie Gao (X)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Yanqin Yang (Y)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China; Department of Radiotherapy, the Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China.

Jia Wang (J)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Lu Zhang (L)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Caifeng Sun (C)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Ying Wang (Y)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Jingkai Zhang (J)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Haoyu Dong (H)

Eight-year Clinical Medicine Education Program, Dalian Medical University, Dalian 116044, China.

Han Zhang (H)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Chuanzhou Gao (C)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Bin Zhang (B)

Department of Radiotherapy, the First Affiliated Hospital, Dalian Medical University, Dalian 116044, China.

Bin Feng (B)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

Weifeng Mao (W)

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. Electronic address: maoweifeng@dmu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Métalloprotéines › Protéines de liaison au fer › Protéines à fer non hème › Ferrosulfoprotéines › Complexe I de la chaîne respiratoire › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Composés chimiques organiques › Amidines › Guanidines › Biguanides › Metformine › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Phénomènes physiologiques › Radiotolérance › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Radiosensibilisants › Inhibition of mitochondria NADH-Ubiquinone...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérocycliques avec 4 noyaux ou plus › Roténone › Inhibition of mitochondria NADH-Ubiquinone...