Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer cells in vitro and in vivo.
Animals
Apoptosis
/ drug effects
Autophagy
/ drug effects
Autophagy-Related Proteins
/ antagonists & inhibitors
Cell Proliferation
/ drug effects
Colorectal Neoplasms
/ pathology
Cysteine Endopeptidases
/ metabolism
Female
Lysosomes
/ drug effects
Mice, Inbred BALB C
Mice, Nude
Microtubule-Associated Proteins
/ metabolism
Protein Binding
/ drug effects
Small Molecule Libraries
/ pharmacology
ATG4B
Anti-tumor
FRET assay
autophagy
cell death
colorectal cancer
delipidation
xenografts
Journal
Autophagy
ISSN: 1554-8635
Titre abrégé: Autophagy
Pays: United States
ID NLM: 101265188
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
pubmed:
4
9
2018
medline:
7
3
2020
entrez:
4
9
2018
Statut:
ppublish
Résumé
Human Atg4 homologs are cysteine proteases, which play key roles in the macroautophagy/autophagy process by cleaving Atg8 homologs for conjugation to lipid membranes and for deconjugation of Atg8 homologs from membranes. Expression of ATG4B is significantly increased in colorectal cancer cells compared to normal cells, suggesting that ATG4B may be important for cancer biology. Inhibition of ATG4B may reduce the autophagy activity, thereby sensitizing cancer cells to therapeutic agents. Thus, developing specific and potent ATG4B inhibitors for research as well as for potential therapeutic uses is highly needed. In this study, we integrated
Identifiants
pubmed: 30176161
doi: 10.1080/15548627.2018.1517073
pmc: PMC6333450
doi:
Substances chimiques
Autophagy-Related Proteins
0
MAP1LC3A protein, human
0
Microtubule-Associated Proteins
0
Small Molecule Libraries
0
ATG4B protein, human
EC 3.4.22.-
Cysteine Endopeptidases
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
295-311Références
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