Setanaxib as a Potent Hypoxia-specific Therapeutic Agent Against Liver Cancer.
Antineoplastic Agents
/ pharmacology
Cell Hypoxia
/ drug effects
Cell Line, Tumor
Humans
Hypoxia
/ metabolism
Liver Neoplasms
/ metabolism
Mitochondria
/ metabolism
NADPH Oxidase 4
/ antagonists & inhibitors
NADPH Oxidases
/ metabolism
Oxidative Stress
/ drug effects
Reactive Oxygen Species
/ metabolism
Cancer treatment
hypoxia
liver cancer
oxidative stress
setanaxib
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
12
06
2020
revised:
30
06
2020
accepted:
01
07
2020
entrez:
4
9
2020
pubmed:
4
9
2020
medline:
20
9
2020
Statut:
ppublish
Résumé
Liver cancer has extremely poor prognosis. The cancerous tissues contain hypoxic regions, and the available drugs are poorly effective in hypoxic environments. NADPH oxidase 4 (NOX4), producing reactive oxygen species (ROS), may contribute to cancer malignancy under hypoxic conditions. However, its role in liver cancer has not been examined in detail. Our aim was to explore the effects of setanaxib, a recently developed selective NOX4 inhibitor, in liver cancer cells under hypoxic conditions. Liver cancer cell lines (HepG2, HLE and Alexander) were treated with hypoxia-mimetic agent cobalt chloride. Cytotoxicity assays, immunoblot analysis and ROS detection assay were performed to detect the effect of setanaxib under hypoxic conditions. Setanaxib exhibited hypoxia-selective cytotoxicity and triggered apoptosis in cancer cells. Moreover, setanaxib caused mitochondrial ROS accumulation under hypoxic conditions. Treatment with antioxidants markedly attenuated setanaxib-induced cytotoxicity and apoptosis under hypoxic conditions. Setanaxib caused mitochondrial ROS accumulation in a hypoxia-selective manner and evoked cancer cell cytotoxicity by inducing apoptosis. Thus, setanaxib has a great potential as a novel anticancer compound under hypoxic conditions.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Liver cancer has extremely poor prognosis. The cancerous tissues contain hypoxic regions, and the available drugs are poorly effective in hypoxic environments. NADPH oxidase 4 (NOX4), producing reactive oxygen species (ROS), may contribute to cancer malignancy under hypoxic conditions. However, its role in liver cancer has not been examined in detail. Our aim was to explore the effects of setanaxib, a recently developed selective NOX4 inhibitor, in liver cancer cells under hypoxic conditions.
MATERIALS AND METHODS
METHODS
Liver cancer cell lines (HepG2, HLE and Alexander) were treated with hypoxia-mimetic agent cobalt chloride. Cytotoxicity assays, immunoblot analysis and ROS detection assay were performed to detect the effect of setanaxib under hypoxic conditions.
RESULTS
RESULTS
Setanaxib exhibited hypoxia-selective cytotoxicity and triggered apoptosis in cancer cells. Moreover, setanaxib caused mitochondrial ROS accumulation under hypoxic conditions. Treatment with antioxidants markedly attenuated setanaxib-induced cytotoxicity and apoptosis under hypoxic conditions.
CONCLUSION
CONCLUSIONS
Setanaxib caused mitochondrial ROS accumulation in a hypoxia-selective manner and evoked cancer cell cytotoxicity by inducing apoptosis. Thus, setanaxib has a great potential as a novel anticancer compound under hypoxic conditions.
Identifiants
pubmed: 32878795
pii: 40/9/5071
doi: 10.21873/anticanres.14510
doi:
Substances chimiques
Antineoplastic Agents
0
Reactive Oxygen Species
0
NADPH Oxidase 4
EC 1.6.3.-
NADPH Oxidases
EC 1.6.3.-
NOX4 protein, human
EC 1.6.3.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5071-5079Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.