Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling.
Adenomatous Polyposis Coli
/ genetics
Adenomatous Polyposis Coli Protein
/ genetics
Animals
Artesunate
/ pharmacology
Carcinogenesis
/ drug effects
Cell Line, Tumor
Cell Nucleus
/ metabolism
Disease Models, Animal
Drug Evaluation, Preclinical
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Knockdown Techniques
Hepatocyte Nuclear Factor 1-alpha
/ genetics
Humans
Intestinal Mucosa
/ drug effects
Male
Mice
Mice, Transgenic
Mutation
Promoter Regions, Genetic
T Cell Transcription Factor 1
/ genetics
Transcriptional Activation
/ drug effects
Wnt Signaling Pathway
/ drug effects
ran GTP-Binding Protein
/ antagonists & inhibitors
Journal
Carcinogenesis
ISSN: 1460-2180
Titre abrégé: Carcinogenesis
Pays: England
ID NLM: 8008055
Informations de publication
Date de publication:
11 02 2021
11 02 2021
Historique:
received:
05
06
2020
revised:
10
07
2020
accepted:
21
07
2020
pubmed:
28
7
2020
medline:
29
6
2021
entrez:
26
7
2020
Statut:
ppublish
Résumé
Artesunate (ART) is a clinically approved antimalarial drug and was revealed as a candidate of colorectal cancer chemopreventive agents in our drug screening system. Here, we aimed to understand the suppressive effects of ART on intestinal tumorigenesis. In vitro, ART reduced T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter transcriptional activity. In vivo, ART inhibited intestinal polyp development. We found that ART reduces TCF1/TCF7 nuclear translocation by binding the Ras-related nuclear protein (RAN), suggesting that ART inhibits TCF/LEF transcriptional factor nuclear translocation by binding to RAN, thereby inhibiting Wnt signaling. Our results provide a novel mechanism through which artesunate inhibits intestinal tumorigenesis.
Identifiants
pubmed: 32710739
pii: 5876350
doi: 10.1093/carcin/bgaa084
doi:
Substances chimiques
Adenomatous Polyposis Coli Protein
0
HNF1A protein, human
0
Hepatocyte Nuclear Factor 1-alpha
0
Hnf1a protein, mouse
0
RAN protein, human
0
Ran protein, mouse
0
T Cell Transcription Factor 1
0
TCF7 protein, human
0
adenomatous polyposis coli protein, mouse
0
Artesunate
60W3249T9M
ran GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
148-158Informations de copyright
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.