Glabrescione B delivery by self-assembling micelles efficiently inhibits tumor growth in preclinical models of Hedgehog-dependent medulloblastoma.
Animals
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Blood-Brain Barrier
/ metabolism
Cell Line, Tumor
Cerebellar Neoplasms
/ drug therapy
Cholanes
/ chemistry
Chromones
/ administration & dosage
Disease Models, Animal
Drug Carriers
/ chemistry
Drug Compounding
/ methods
Drug Liberation
Drug Screening Assays, Antitumor
Female
Hedgehog Proteins
/ antagonists & inhibitors
Humans
Male
Medulloblastoma
/ drug therapy
Mice
Mice, Transgenic
Micelles
Polyethylene Glycols
/ chemistry
Primary Cell Culture
Signal Transduction
/ drug effects
Tissue Distribution
Drug delivery
GLI inhibitor
Hedgehog signaling pathway
Medulloblastoma
Pharmacology
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
28 02 2021
28 02 2021
Historique:
received:
21
08
2020
revised:
20
11
2020
accepted:
23
11
2020
pubmed:
30
11
2020
medline:
21
5
2021
entrez:
29
11
2020
Statut:
ppublish
Résumé
Aberrant activation of the Hedgehog (Hh) pathway leads to the development of several tumors, including medulloblastoma (MB), the most common pediatric brain malignancy. Hh inhibitors acting on GLI1, the final effector of Hh signaling, offer a valuable opportunity to overcome the pitfalls of the existing therapies to treat Hh-driven cancers. In this study, the toxicity, delivery, biodistribution, and anticancer efficacy of Glabrescione B (GlaB), a selective GLI1 inhibitor, were investigated in preclinical models of Hh-dependent MB. To overcome its poor water solubility, GlaB was formulated with a self-assembling amphiphilic polymer forming micelles, called mPEG
Identifiants
pubmed: 33249196
pii: S0304-3835(20)30626-1
doi: 10.1016/j.canlet.2020.11.028
pii:
doi:
Substances chimiques
Atoh1 protein, mouse
0
Basic Helix-Loop-Helix Transcription Factors
0
Cholanes
0
Chromones
0
Drug Carriers
0
Hedgehog Proteins
0
Micelles
0
Shh protein, mouse
0
glabrescione B
0
Polyethylene Glycols
3WJQ0SDW1A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
220-231Informations de copyright
Copyright © 2020. Published by Elsevier B.V.