Activation of LXRβ inhibits tumor respiration and is synthetically lethal with Bcl-xL inhibition.
Animals
Apoptosis
/ drug effects
Benzoates
/ metabolism
Benzylamines
/ metabolism
Carcinoma
/ drug therapy
Cell Proliferation
/ drug effects
Cell Respiration
/ drug effects
Disease Models, Animal
Gene Expression Profiling
Glioblastoma
/ drug therapy
Humans
Indazoles
/ metabolism
Liver X Receptors
/ agonists
Melanoma
/ drug therapy
Metabolomics
Models, Theoretical
Treatment Outcome
bcl-X Protein
/ antagonists & inhibitors
BH3 mimetics
LXR agonist
colon adenocarcinoma
electron transport chain
glioblastoma
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
17
04
2019
revised:
01
08
2019
accepted:
06
08
2019
pubmed:
31
8
2019
medline:
17
4
2020
entrez:
31
8
2019
Statut:
ppublish
Résumé
Liver-X-receptor (LXR) agonists are known to bear anti-tumor activity. However, their efficacy is limited and additional insights regarding the underlying mechanism are necessary. By performing transcriptome analysis coupled with global polar metabolite screening, we show that LXR agonists, LXR623 and GW3965, enhance synergistically the anti-proliferative effect of BH3 mimetics in solid tumor malignancies, which is predominantly mediated by cell death with features of apoptosis and is rescued by exogenous cholesterol. Extracellular flux analysis and carbon tracing experiments (U-
Identifiants
pubmed: 31468706
doi: 10.15252/emmm.201910769
pmc: PMC6783693
doi:
Substances chimiques
2-(2-chloro-4-fluorobenzyl)-3-(4-fluorophenyl)-7-(trifluoromethyl)-2H-indazole
0
BCL2L1 protein, human
0
Benzoates
0
Benzylamines
0
GW 3965
0
Indazoles
0
Liver X Receptors
0
bcl-X Protein
0
Banques de données
GEO
['GSE110151', 'GSE110152']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e10769Subventions
Organisme : NINDS NIH HHS
ID : R01 NS095848
Pays : United States
Organisme : HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : R01NS102366
Pays : International
Organisme : CTSA
ID : UL1-TR001430
Pays : International
Organisme : NINDS NIH HHS
ID : K08 NS083732
Pays : United States
Organisme : Cancer Center Flow Core Facility funded in part through Center Grant
ID : P30CA013696
Pays : International
Organisme : American Brain Tumor Association (ABTA)
ID : BRF1900018
Pays : International
Organisme : HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : K08NS083732
Pays : International
Organisme : NINDS NIH HHS
ID : R01 NS102366
Pays : United States
Organisme : HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : R01NS095848
Pays : International
Organisme : American Brain Tumor Association (ABTA)
ID : DG1700013
Pays : International
Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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