1H-NMR spectroscopy
Glioma
Hh pathway
Isoflavones
Metabolomics
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
28 08 2019
28 08 2019
Historique:
received:
13
06
2019
accepted:
14
08
2019
entrez:
29
8
2019
pubmed:
29
8
2019
medline:
10
9
2020
Statut:
epublish
Résumé
Glioma is the most common and primary brain tumors in adults. Despite the available multimodal therapies, glioma patients appear to have a poor prognosis. The Hedgehog (Hh) signaling is involved in tumorigenesis and emerged as a promising target for brain tumors. Glabrescione B (GlaB) has been recently identified as the first direct inhibitor of Gli1, the downstream effector of the pathway. We established the overexpression of Gli1 in murine glioma cells (GL261) and GlaB effect on cell viability. We used We found that GlaB affected the growth of murine glioma cells both in vitro and in vivo animal model. Using an untargeted Our results indicate that GlaB inhibits glioma cell growth and exacerbates Warburg effect, increasing lactate production. In addition, the simultaneous blockade of Gli1 and lactate efflux amplifies the anti-tumor effect in vivo, providing new potential therapeutic strategy for this brain tumor.
Sections du résumé
BACKGROUND
Glioma is the most common and primary brain tumors in adults. Despite the available multimodal therapies, glioma patients appear to have a poor prognosis. The Hedgehog (Hh) signaling is involved in tumorigenesis and emerged as a promising target for brain tumors. Glabrescione B (GlaB) has been recently identified as the first direct inhibitor of Gli1, the downstream effector of the pathway.
METHODS
We established the overexpression of Gli1 in murine glioma cells (GL261) and GlaB effect on cell viability. We used
RESULTS
We found that GlaB affected the growth of murine glioma cells both in vitro and in vivo animal model. Using an untargeted
CONCLUSIONS
Our results indicate that GlaB inhibits glioma cell growth and exacerbates Warburg effect, increasing lactate production. In addition, the simultaneous blockade of Gli1 and lactate efflux amplifies the anti-tumor effect in vivo, providing new potential therapeutic strategy for this brain tumor.
Identifiants
pubmed: 31455353
doi: 10.1186/s12964-019-0421-8
pii: 10.1186/s12964-019-0421-8
pmc: PMC6712882
doi:
Substances chimiques
Chromones
0
glabrescione B
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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