Titre
Cardamonin, a chalcone, inhibits human triple negative breast cancer cell invasiveness by downregulation of Wnt/β-catenin signaling cascades and reversal of epithelial-mesenchymal transition.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Shrivastava, S.
Auteure/Auteur
Jeengar, M.K.
Auteure/Auteur
Thummuri, D.
Auteure/Auteur
Koval, A.
Auteure/Auteur
Katanaev, V.L.
Auteure/Auteur
Marepally, S.
Auteure/Auteur
Naidu, VGM
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1872-8081
Statut éditorial
Publié
Date de publication
2017-03
Volume
43
Numéro
2
Première page
152
Dernière page/numéro d’article
169
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Cardamonin (CD), an active chalconoid, has shown potent anticancer effects in preclinical studies; however, the effect and underlying mechanism of CD for the treatment of triple negative breast cancer (TNBC) is unclear. This study aims to examine the cytotoxic effects of CD and investigate the underlying mechanism in human TNBC cells. The results show that CD exhibits cytotoxicity by inducing apoptosis and cell cycle arrest in TNBC cells via modulation of Bcl-2, Bax, cyt-C, cleaved caspase-3, and PARP. We find that CD significantly increases expression of the epithelial marker E-cadherin, while reciprocally decreasing expression of mesenchymal markers such as snail, slug, and vimentin in BT-549 cells. In parallel with epithelial-mesenchymal transition (EMT) reversal, CD down regulates invasion and migration of BT-549 cells. CD markedly reduces stability and nuclear translocation of β-catenin, accompanied with downregulation of β-catenin target genes. Using the TopFlash luciferase reporter assay, we reveal CD as a specific inhibitor of the Wnt3a-induced signaling. These results suggest the involvement of the Wnt/β-catenin signaling in the CD-induced EMT reversion of BT-549 cells. Notably, CD restores the glycogen synthase kinase-3β (GSK3β) activity, required for β-catenin destruction via the proteasome-mediated system, by inhibiting the phosphorylation of GSK3β by Akt. These occurrences ultimately lead to the blockage of EMT and the invasion of TNBC cells. Further antitumor activity of CD was tested in 4T1 (TNBC cells) induced tumor and it was found that CD significantly inhibited the tumor volume at dose of 5 mg/kg-treated mice. © 2016 BioFactors, 43(2):152-169, 2017.
Sujets
PID Serval
serval:BIB_A9FC3CE7A92D
PMID
Date de création
2016-09-21T16:46:23.518Z
Date de création dans IRIS
2025-05-20T22:11:59Z