Anti-tumor Activity of the Small Molecule Inhibitor PRI-724 Against β-Catenin-activated Hepatocellular Carcinoma.
Antineoplastic Agents
/ pharmacology
Biomarkers
Bridged Bicyclo Compounds, Heterocyclic
/ pharmacology
Carcinoma, Hepatocellular
/ drug therapy
Cell Cycle
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Gene Expression
Humans
Immunohistochemistry
Liver Neoplasms
/ drug therapy
Pyrimidinones
/ pharmacology
Wnt Proteins
/ metabolism
beta Catenin
/ antagonists & inhibitors
CBP
Hepatocellular carcinoma
PRI-724
Wnt
inhibitor
β-catenin
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
21
07
2020
revised:
25
07
2020
accepted:
27
07
2020
entrez:
4
9
2020
pubmed:
4
9
2020
medline:
20
9
2020
Statut:
ppublish
Résumé
CBP is a transcriptional coactivator in the Wnt/β-catenin pathway that is related to cell kinetics and differentiation. This study aimed to characterize β-catenin-activated hepatocellular carcinoma (HCC) and evaluate the direct effects of PRI-724 (a selective inhibitor of Wnt/β-catenin/CBP signaling) on HCC. Immunohistochemistry for β-catenin was performed in 199 HCC resected samples. Moreover, using cultured HCC cell lines, cell kinetics and its related proteins were analyzed after treatment of cells with C-82 (active form of PRI-724). Nuclear β-catenin expression was found in 18% of HCC cases and the tumor sizes in these positive samples were larger. In HCC cell lines with a constitutively activated β-catenin, C-82 inhibited cell proliferation. C-82 led to an increase in the percentage of cells in the G PRI-724(C-82) may be a novel drug for β-catenin-activated HCC therapy.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
CBP is a transcriptional coactivator in the Wnt/β-catenin pathway that is related to cell kinetics and differentiation. This study aimed to characterize β-catenin-activated hepatocellular carcinoma (HCC) and evaluate the direct effects of PRI-724 (a selective inhibitor of Wnt/β-catenin/CBP signaling) on HCC.
MATERIALS AND METHODS
METHODS
Immunohistochemistry for β-catenin was performed in 199 HCC resected samples. Moreover, using cultured HCC cell lines, cell kinetics and its related proteins were analyzed after treatment of cells with C-82 (active form of PRI-724).
RESULTS
RESULTS
Nuclear β-catenin expression was found in 18% of HCC cases and the tumor sizes in these positive samples were larger. In HCC cell lines with a constitutively activated β-catenin, C-82 inhibited cell proliferation. C-82 led to an increase in the percentage of cells in the G
CONCLUSION
CONCLUSIONS
PRI-724(C-82) may be a novel drug for β-catenin-activated HCC therapy.
Identifiants
pubmed: 32878809
pii: 40/9/5211
doi: 10.21873/anticanres.14524
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers
0
Bridged Bicyclo Compounds, Heterocyclic
0
ICG 001
0
Pyrimidinones
0
Wnt Proteins
0
beta Catenin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5211-5219Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.