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

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

  • Koval AV Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne 1005, Switzerland.
  • Vlasov P Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) 88 Dr. Aiguader, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
  • Shichkova P Moscow Institute of Physics and Technology (State University), Moscow, Russia.
  • Khunderyakova S Municipal budget institution of general education gymnasium "Pushchino", Pushchino, Russia.
  • Markov Y National Research University Higher School of Economics, Moscow, Russia.
  • Panchenko J Moscow Institute of Physics and Technology (State University), Moscow, Russia.
  • Volodina A Kazan Federal University, Kazan, Russia.
  • Kondrashov FA Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) 88 Dr. Aiguader, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 23 Pg. Lluís Companys, 08010 Barcelona, Spain.
  • Katanaev VL Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne 1005, Switzerland; Institute of Protein Research, Russian Academy of Science, Instituskaya 4, Moscow Region, Pushchino 142290, Russia. Electronic address: vladimir.katanaev@unil.ch.
Show more…
  • 2013-12-21
Published in:
  • Biochemical pharmacology. - 2014
Breast cancer
Clofazimine
In silico screening
Wnt signaling
Animals
Binding Sites
Cell Line, Tumor
Clofazimine
Crystallography, X-Ray
Growth Inhibitors
HEK293 Cells
Humans
Leprostatic Agents
Mice
Triple Negative Breast Neoplasms
Wnt Signaling Pathway
Wnt3A Protein
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/265069
Statistics
Document views: 17 File downloads: