Co-inhibition of BET proteins and PI3Kα triggers mitochondrial apoptosis in rhabdomyosarcoma cells.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Apoptosis
/ drug effects
Azepines
/ pharmacology
Bcl-2-Like Protein 11
/ genetics
Drug Synergism
Gene Expression Regulation, Neoplastic
/ genetics
Histone Deacetylase Inhibitors
/ pharmacology
Humans
Mice
Mitochondria
/ drug effects
Myeloid Cell Leukemia Sequence 1 Protein
/ genetics
Proto-Oncogene Proteins c-bcl-2
/ genetics
RNA-Seq
Rhabdomyosarcoma
/ drug therapy
Thiazoles
/ pharmacology
Transcription Factors
/ antagonists & inhibitors
Triazoles
/ pharmacology
bcl-X Protein
/ genetics
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
10
01
2019
accepted:
17
02
2020
revised:
14
02
2020
pubmed:
13
3
2020
medline:
26
11
2020
entrez:
13
3
2020
Statut:
ppublish
Résumé
Remodeling transcription by targeting bromodomain and extraterminal (BET) proteins has emerged as promising anticancer strategy. Here, we identify a novel synergistic interaction of the BET inhibitor JQ1 with the PI3Kα-specific inhibitor BYL719 to trigger mitochondrial apoptosis and to suppress tumor growth in models of rhabdomyosarcoma (RMS). RNA-Seq revealed that JQ1/BYL719 co-treatment shifts the overall balance of BCL-2 family gene expression towards apoptosis and upregulates expression of BMF, BCL2L11 (BIM), and PMAIP1 (NOXA) while downregulating BCL2L1 (BCL-x
Identifiants
pubmed: 32161312
doi: 10.1038/s41388-020-1229-0
pii: 10.1038/s41388-020-1229-0
doi:
Substances chimiques
(+)-JQ1 compound
0
Adaptor Proteins, Signal Transducing
0
Azepines
0
BCL2 protein, human
0
BCL2L11 protein, human
0
BMF protein, human
0
Bcl-2-Like Protein 11
0
Histone Deacetylase Inhibitors
0
MCL1 protein, human
0
Myeloid Cell Leukemia Sequence 1 Protein
0
PI3KCA protein, human
0
PMAIP1 protein, human
0
Proto-Oncogene Proteins c-bcl-2
0
Thiazoles
0
Transcription Factors
0
Triazoles
0
bcl-X Protein
0
Alpelisib
08W5N2C97Q
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3837-3852Références
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