Imiquimod-induced ROS production disrupts the balance of mitochondrial dynamics and increases mitophagy in skin cancer cells.
Animals
Antineoplastic Agents
/ pharmacology
Antioxidants
/ pharmacology
Cell Line, Tumor
Cell Survival
/ drug effects
Free Radical Scavengers
/ pharmacology
Humans
Imiquimod
/ pharmacology
Keratinocytes
Mice
Mitochondria
/ drug effects
Mitochondrial Dynamics
/ drug effects
Mitophagy
/ drug effects
Primary Cell Culture
Reactive Oxygen Species
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Skin Neoplasms
/ drug therapy
Imiquimod
Mitochondrial dynamics
Mitophagy
ROS (reactive oxygen species)
Journal
Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
25
11
2019
revised:
10
03
2020
accepted:
31
03
2020
pubmed:
8
5
2020
medline:
15
4
2021
entrez:
8
5
2020
Statut:
ppublish
Résumé
Mitochondrial homeostasis is a highly dynamic process involving continuous fission and fusion cycles and mitophagy to maintain mitochondrial functionality. Imiquimod (IMQ), a Toll-like receptor (TLR) 7 ligand, is used to treat various skin malignancies. IMQ also induces apoptotic and autophagic cell death in various cancers through a TLR7-independent pathway. To investigate whether IMQ-induced ROS production is involved in mitochondrial dysfunction, mitochondrial fragmentation and mitophagy in skin cancer cells. BCC/KMC-1, B16F10 and A375 skin cancer cells, AGS gastric cancer cells and primary human keratinocytes were treated with 50 μg/mL IMQ. After 4 h, ROS were detected by CM-H IMQ not only induced severe ROS production but also resulted in increased mitochondrial membrane potential loss, mitochondrial fission and mitophagy and decreased oxygen consumption in skin cancer cells compared with normal keratinocytes. Pretreatment with the antioxidant NAC reduced IMQ-induced ROS production and attenuated IMQ-induced mitochondrial fission and mitophagy in skin cancer cells. IMQ-induced ROS might be associated with mitochondrial dysfunction, mitochondrial fission and mitophagy in cancer cells. Alleviating IMQ-induced ROS production would reduce mitochondrial fission-to-fusion skewing and further reduce IMQ-induced mitophagy.
Sections du résumé
BACKGROUND
BACKGROUND
Mitochondrial homeostasis is a highly dynamic process involving continuous fission and fusion cycles and mitophagy to maintain mitochondrial functionality. Imiquimod (IMQ), a Toll-like receptor (TLR) 7 ligand, is used to treat various skin malignancies. IMQ also induces apoptotic and autophagic cell death in various cancers through a TLR7-independent pathway.
OBJECTIVE
OBJECTIVE
To investigate whether IMQ-induced ROS production is involved in mitochondrial dysfunction, mitochondrial fragmentation and mitophagy in skin cancer cells.
METHODS
METHODS
BCC/KMC-1, B16F10 and A375 skin cancer cells, AGS gastric cancer cells and primary human keratinocytes were treated with 50 μg/mL IMQ. After 4 h, ROS were detected by CM-H
RESULTS
RESULTS
IMQ not only induced severe ROS production but also resulted in increased mitochondrial membrane potential loss, mitochondrial fission and mitophagy and decreased oxygen consumption in skin cancer cells compared with normal keratinocytes. Pretreatment with the antioxidant NAC reduced IMQ-induced ROS production and attenuated IMQ-induced mitochondrial fission and mitophagy in skin cancer cells.
CONCLUSIONS
CONCLUSIONS
IMQ-induced ROS might be associated with mitochondrial dysfunction, mitochondrial fission and mitophagy in cancer cells. Alleviating IMQ-induced ROS production would reduce mitochondrial fission-to-fusion skewing and further reduce IMQ-induced mitophagy.
Identifiants
pubmed: 32376151
pii: S0923-1811(20)30133-X
doi: 10.1016/j.jdermsci.2020.03.009
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Antioxidants
0
Free Radical Scavengers
0
Reactive Oxygen Species
0
Imiquimod
P1QW714R7M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
152-162Informations de copyright
Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no conflicts of interest to declare.