Anti-leprosy drug clofazimine inhibits growth of triple-negative breast cancer cells via inhibition of canonical Wnt signaling.

Détails

ID Serval
serval:BIB_083381A0D59E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Anti-leprosy drug clofazimine inhibits growth of triple-negative breast cancer cells via inhibition of canonical Wnt signaling.
Périodique
Biochemical Pharmacology
Auteur(s)
Koval A.V., Vlasov P., Shichkova P., Khunderyakova S., Markov Y., Panchenko J., Volodina A., Kondrashov F.A., Katanaev V.L.
ISSN
1873-2968 (Electronic)
ISSN-L
0006-2952
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
87
Numéro
4
Pages
571-578
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
Research on existing drugs often discovers novel mechanisms of their action and leads to the expansion of their therapeutic scope and subsequent remarketing. The Wnt signaling pathway is of the immediate therapeutic relevance, as it plays critical roles in cancer development and progression. However, drugs which disrupt this pathway are unavailable despite the high demand. Here we report an attempt to identify antagonists of the Wnt-FZD interaction among the library of the FDA-approved drugs. We performed an in silico screening which brought up several potential antagonists of the ligand-receptor interaction. 14 of these substances were tested using the TopFlash luciferase reporter assay and four of them identified as active and specific inhibitors of the Wnt3a-induced signaling. However, further analysis through GTP-binding and β-catenin stabilization assays showed that the compounds do not target the Wnt-FZD pair, but inhibit the signaling at downstream levels. We further describe the previously unknown inhibitory activity of an anti-leprosy drug clofazimine in the Wnt pathway and provide data demonstrating its efficiency in suppressing growth of Wnt-dependent triple-negative breast cancer cells. These data provide a basis for further investigations of the efficiency of clofazimine in treatment of Wnt-dependent cancers.
Mots-clé
Animals, Binding Sites/drug effects, Binding Sites/physiology, Cell Line, Tumor, Clofazimine/pharmacology, Clofazimine/therapeutic use, Crystallography, X-Ray, Growth Inhibitors/pharmacology, Growth Inhibitors/therapeutic use, HEK293 Cells, Humans, Leprostatic Agents/pharmacology, Leprostatic Agents/therapeutic use, Mice, Triple Negative Breast Neoplasms/chemistry, Triple Negative Breast Neoplasms/drug therapy, Wnt Signaling Pathway/drug effects, Wnt Signaling Pathway/physiology, Wnt3A Protein/antagonists & inhibitors, Wnt3A Protein/chemistry
Pubmed
Web of science
Création de la notice
10/10/2016 10:33
Dernière modification de la notice
20/08/2019 12:30
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