Aspalathin-rich green Aspalathus linearis extract suppresses migration and invasion of human castration-resistant prostate cancer cells via inhibition of YAP signaling.
Adaptor Proteins, Signal Transducing
/ antagonists & inhibitors
Antineoplastic Agents, Phytogenic
/ chemistry
Aspalathus
/ chemistry
Cell Line, Tumor
Cell Movement
/ drug effects
Chalcones
/ pharmacology
Humans
Male
Paxillin
/ metabolism
Plant Extracts
/ chemistry
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Transcription Factors
/ antagonists & inhibitors
YAP-Signaling Proteins
Aspalathin
Invasion
Migration
Prostate cancer
Rooibos
YAP
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
16
12
2019
revised:
28
02
2020
accepted:
16
03
2020
pubmed:
29
3
2020
medline:
4
8
2020
entrez:
29
3
2020
Statut:
ppublish
Résumé
More than 80% of advanced prostate cancer (PCa) cases have bone metastasis, with a 5-year survival rate of 25%. Previously, we reported that GRT, a standardized, pharmaceutical-grade aspalathin-rich extract (12.78 g aspalathin/100 g extract), prepared from green rooibos produced from the leaves and fine stems of Aspalathus linearis, inhibits the proliferation of PCa cells, meriting this investigation to determine if GRT can suppress the migration and invasion of castration-resistant prostate cancer (CRPC) cells. In the present study, we investigated whether GRT extract can interfere with the migration and invasion of human CRPC cells. Transwell assays were used to explore the effects of GRT on the migration and invasion of CRPC cells. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism(s). Treatment with 25-100 μg/ml GRT suppressed the migration and invasion of LNCaP C4-2B and 22Rv1 CRPC cells. MWA and Western blot analysis indicated that GRT treatment suppressed the protein level of yes-associated protein (YAP), macrophage stimulating 1 protein (MST1), phospho-MST1/phospho-MST2 T183/T180, and paxillin, but increased the abundance of E-cadherin. Over-expression of YAP rescued the suppressive effects of GRT on migration and invasion of CRPC cells. Treatment with the major flavonoid of GRT - the C-glucosyl dihydrochalcone, aspalathin - at a concentration of 75-100 μg/ml also reduced the migration and invasion of CRPC cells, and the inhibition was partially rescued by YAP over-expression. GRT treatment suppresses the migration and invasion of CRPC cells via inhibition of YAP signaling and paxillin.
Sections du résumé
BACKGROUND
BACKGROUND
More than 80% of advanced prostate cancer (PCa) cases have bone metastasis, with a 5-year survival rate of 25%. Previously, we reported that GRT, a standardized, pharmaceutical-grade aspalathin-rich extract (12.78 g aspalathin/100 g extract), prepared from green rooibos produced from the leaves and fine stems of Aspalathus linearis, inhibits the proliferation of PCa cells, meriting this investigation to determine if GRT can suppress the migration and invasion of castration-resistant prostate cancer (CRPC) cells.
PURPOSE
OBJECTIVE
In the present study, we investigated whether GRT extract can interfere with the migration and invasion of human CRPC cells.
METHODS
METHODS
Transwell assays were used to explore the effects of GRT on the migration and invasion of CRPC cells. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism(s).
RESULTS
RESULTS
Treatment with 25-100 μg/ml GRT suppressed the migration and invasion of LNCaP C4-2B and 22Rv1 CRPC cells. MWA and Western blot analysis indicated that GRT treatment suppressed the protein level of yes-associated protein (YAP), macrophage stimulating 1 protein (MST1), phospho-MST1/phospho-MST2 T183/T180, and paxillin, but increased the abundance of E-cadherin. Over-expression of YAP rescued the suppressive effects of GRT on migration and invasion of CRPC cells. Treatment with the major flavonoid of GRT - the C-glucosyl dihydrochalcone, aspalathin - at a concentration of 75-100 μg/ml also reduced the migration and invasion of CRPC cells, and the inhibition was partially rescued by YAP over-expression.
CONCLUSIONS
CONCLUSIONS
GRT treatment suppresses the migration and invasion of CRPC cells via inhibition of YAP signaling and paxillin.
Identifiants
pubmed: 32217447
pii: S0944-7113(20)30040-4
doi: 10.1016/j.phymed.2020.153210
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antineoplastic Agents, Phytogenic
0
Chalcones
0
PXN protein, human
0
Paxillin
0
Plant Extracts
0
Transcription Factors
0
YAP-Signaling Proteins
0
YAP1 protein, human
0
aspalathin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153210Informations de copyright
Copyright © 2020. Published by Elsevier GmbH.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The NRF grant holder (CJF Muller) acknowledges that opinions, findings, and conclusions or recommendations expressed in any publication generated by the NRF-supported research are those of the authors, and that the NRF accepts no liability whatsoever in this regard. The funding bodies had no involvement in the study design, collection, analysis and interpretation of data, writing of the manuscript, or decision to publish the work.