Amentoflavone, active compound of Selaginella tamariscina, inhibits in vitro and in vivo TGF-β-induced metastasis of human cancer cells.
A549 Cells
Animals
Antigens, CD
/ metabolism
Antineoplastic Agents
/ pharmacology
Biflavonoids
/ pharmacology
Cadherins
/ metabolism
Cell Movement
/ drug effects
Epithelial-Mesenchymal Transition
/ drug effects
Humans
Lung Neoplasms
/ drug therapy
Mice, SCID
Neoplasm Metastasis
/ prevention & control
Nuclear Proteins
/ metabolism
Plant Extracts
/ pharmacology
Selaginellaceae
/ chemistry
Snail Family Transcription Factors
/ metabolism
Transforming Growth Factor beta
/ pharmacology
Twist-Related Protein 1
/ metabolism
Amentoflavone
E-cadherin
Epithelial-to-mesenchymal transition
Metastasis animal model
Selaginella tamariscina
Journal
Archives of biochemistry and biophysics
ISSN: 1096-0384
Titre abrégé: Arch Biochem Biophys
Pays: United States
ID NLM: 0372430
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
29
01
2020
revised:
06
04
2020
accepted:
16
04
2020
pubmed:
29
4
2020
medline:
3
10
2020
entrez:
29
4
2020
Statut:
ppublish
Résumé
Epithelial mesenchymal transition (EMT) is a well-known and important step in metastasis and thus can be a key target in cancer treatment. Here, we tested the EMT inhibitory actions of Selaginella tamariscina and its active component, amentoflavone (AF). EMT was examined in vitro using wound-healing and invasion assays and by monitoring changes in the expression of the EMT-related proteins, E-cadherin, Snail, and Twist. Metastasis was examined in vivo using SCID mice injected with luciferase-labeled A549 cells. We confirmed that aqueous extracts of S. tamariscina (STE) and AF inhibited EMT in human cancer cell lines. We found that STE and AF at nontoxic concentrations exerted remarkable inhibitory effects on migration (wound healing assay) and invasion (Transwell assay) in tumor necrosis factor (TGF)-β-treated cancer cells. Western blotting and immunofluorescence imaging show that AF treatment also restored E-cadherin expression in these cells compared to cells treated with TGF-β only. Suppression of metastasis by AF was investigated by monitoring migration of tail-vein-injected, circulating A549-luc cells to the lungs in mice. After 3 wk, fewer nodules were observed in mice co-treated with AF compared with those treated with TGF-β only. Our findings indicate that STE and AF are promising EMT inhibitors and, ultimately, potentially potent antitumor agents.
Identifiants
pubmed: 32343974
pii: S0003-9861(20)30393-3
doi: 10.1016/j.abb.2020.108384
pii:
doi:
Substances chimiques
Antigens, CD
0
Antineoplastic Agents
0
Biflavonoids
0
CDH1 protein, human
0
Cadherins
0
Nuclear Proteins
0
Plant Extracts
0
SNAI1 protein, human
0
Snail Family Transcription Factors
0
TWIST1 protein, human
0
Transforming Growth Factor beta
0
Twist-Related Protein 1
0
amentoflavone
9I1VC79L77
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108384Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no competing financial interests.