Evidence of a dual mechanism of action underlying the anti-proliferative and cytotoxic effects of ammonium-alkyloxy-stilbene-based α7- and α9-nicotinic ligands on glioblastoma cells.
Adenosine Triphosphate
/ metabolism
Ammonium Compounds
/ pharmacology
Animals
Antineoplastic Agents
/ pharmacology
Astrocytes
/ drug effects
Brain Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Physiological Phenomena
/ drug effects
Glioblastoma
/ drug therapy
Humans
Ligands
Mice
Proto-Oncogene Proteins c-akt
/ metabolism
Reactive Oxygen Species
/ metabolism
Receptors, Nicotinic
/ genetics
Stilbenes
/ pharmacology
alpha7 Nicotinic Acetylcholine Receptor
/ genetics
AKT1
ATP
Acetylcholine
Apoptosis
Cell cycle
Glioblastoma cell lines
H2DCFDA
MG624
Nicotine
Oxystilbene
PNU120596
Proliferation
StN-4
StN-8
tert-butyl hydroperoxide
tetramethylrhodamine, methyl ester
α7/α9 neuronal nicotinic receptors
αBungarotoxin
Journal
Pharmacological research
ISSN: 1096-1186
Titre abrégé: Pharmacol Res
Pays: Netherlands
ID NLM: 8907422
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
05
08
2021
revised:
27
09
2021
accepted:
23
10
2021
pubmed:
11
11
2021
medline:
19
3
2022
entrez:
10
11
2021
Statut:
ppublish
Résumé
Glioblastomas (GBMs), the most frequent brain tumours, are highly invasive and their prognosis is still poor despite the use of combination treatment. MG624 is a 4-oxystilbene derivative that is active on α7- and α9-containing neuronal nicotinic acetylcholine receptor (nAChR) subtypes. Hybridisation of MG624 with a non-nicotinic resveratrol-derived pro-oxidant mitocan has led to two novel compounds (StN-4 and StN-8) that are more potent than MG624 in reducing the viability of GBM cells, but less potent in reducing the viability of mouse astrocytes. Functional analysis of their activity on α7 receptors showed that StN-4 is a silent agonist, whereas StN-8 is a full antagonist, and neither alters intracellular [Ca
Identifiants
pubmed: 34756924
pii: S1043-6618(21)00543-0
doi: 10.1016/j.phrs.2021.105959
pii:
doi:
Substances chimiques
Ammonium Compounds
0
Antineoplastic Agents
0
CHRNA9 protein, human
0
Ligands
0
Reactive Oxygen Species
0
Receptors, Nicotinic
0
Stilbenes
0
alpha7 Nicotinic Acetylcholine Receptor
0
Adenosine Triphosphate
8L70Q75FXE
AKT1 protein, human
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105959Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.