Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF)

Vancauwenberghe, Eric; Noyer, Lucile; Derouiche, Sandra; Lemonnier, Loïc; Gosset, Pierre, Dr; Sadofsky, Laura R.; Mariot, Pascal; Warnier, Marine; Bokhobza, Alexandre; Slomianny, Christian; Mauroy, Brigitte; Bonnal, Jean-Louis; Dewailly, Etienne; Delcourt, Philippe; Allart, Laurent; Prevarskaya, Natalia; Roudbaraki, Morad

Hull York Medical School
TRPA1; Prostate cancer; Tumour microenvironment; Resveratrol; Apoptosis
2017

Journal article


Rights
©2018 University of Hull
Alternative title
Resveratrol activates CAF TRPA1
Abstract

Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors. However, the effects of RES on PCa CAF have not been studied so far. We have investigated here for the first time the effects of RES on the physiology of PCa CAF in the context of TME. Using a prostate cancer CAF cell line and primary cultures of CAF from prostate cancers, we show that RES activates the N-terminal mutated Transient Receptor Potential Ankyrin 1 (TRPA1) channel leading to an increase in intracellular calcium concentration and the expression and secretion of growth factors (HGF and VEGF) without inducing apoptosis in these cells. Interestingly, in the present work, we also show that when the prostate cancer cells were co-cultured with CAF, the RES-induced cancer cell apoptosis was reduced by 40%, an apoptosis reduction canceled in the presence of the TRPA1 channel inhibitors. The present work highlights CAF TRPA1 ion channels as a target for RES and the importance of the channel in the epithelial-stromal crosstalk in the TME leading to resistance to the RES-induced apoptosis.

Publisher
The University of Hull
Peer reviewed
Yes
Language
English
Extent
582 KB
Identifier
hull:14581

Journal

Journal title
Molecular carcinogenesis
Publication date
2017
Publisher
Wiley
DOI
10.1002/mc.22642
ISSN (Print)
0899-1987
ISSN (Electronic)
1098-2744
Volume
56
Issue
8
Start page
1851
End page
1867
Notes

This is a description of an article which has been published in: Molecular carcinogenesis, 2017

Link
Published article
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