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.

Détails

ID Serval
serval:BIB_A9FC3CE7A92D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
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.
Périodique
BioFactors (Oxford, England)
Auteur(s)
Shrivastava S., Jeengar M.K., Thummuri D., Koval A., Katanaev V.L., Marepally S., Naidu VGM
ISSN
1872-8081 (Electronic)
ISSN-L
0951-6433
Statut éditorial
Publié
Date de publication
03/2017
Peer-reviewed
Oui
Volume
43
Numéro
2
Pages
152-169
Langue
anglais
Notes
Publication types: Journal Article
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.

Mots-clé
Animals, Apoptosis/drug effects, Cell Line, Tumor, Cell Proliferation/drug effects, Chalcones/administration & dosage, Epithelial-Mesenchymal Transition/drug effects, Female, Gene Expression Regulation, Neoplastic/drug effects, Glycogen Synthase Kinase 3 beta/biosynthesis, Humans, Mice, Neoplasm Invasiveness/genetics, Neoplasm Proteins/biosynthesis, Triple Negative Breast Neoplasms/drug therapy, Triple Negative Breast Neoplasms/genetics, Triple Negative Breast Neoplasms/pathology, Wnt Signaling Pathway/drug effects, Xenograft Model Antitumor Assays
Pubmed
Création de la notice
21/09/2016 17:46
Dernière modification de la notice
20/08/2019 15:14
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