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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; Sadofsky, Laura R.; Mariot, Pascal; Warnier, Marine; Bokhobza, Alexandre; Slomianny, Christian; Mauroy, Brigitte; Bonnal, Jean-Louis; Dewailly, Etienne; Delcourt, Philippe; Allart, Laurent; Desruelles, Emilie; Prevarskaya, Natalia; Roudbaraki, Morad

Authors

Eric Vancauwenberghe

Lucile Noyer

Sandra Derouiche

Loïc Lemonnier

Pierre Gosset

Dr Laura Sadofsky L.R.Sadofsky@hull.ac.uk
Lecturer in Respiratory Medicine/ Academic lead for postgraduate training in HYMS

Pascal Mariot

Marine Warnier

Alexandre Bokhobza

Christian Slomianny

Brigitte Mauroy

Jean-Louis Bonnal

Etienne Dewailly

Philippe Delcourt

Laurent Allart

Emilie Desruelles

Natalia Prevarskaya

Morad Roudbaraki



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.

Journal Article Type Article
Publication Date Aug 1, 2017
Journal Molecular Carcinogenesis
Print ISSN 0899-1987
Electronic ISSN 1098-2744
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 56
Issue 8
Pages 1851-1867
APA6 Citation Vancauwenberghe, E., Noyer, L., Derouiche, S., Lemonnier, L., Gosset, P., Sadofsky, L. R., …Roudbaraki, M. (2017). Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF). Molecular Carcinogenesis, 56(8), 1851-1867. https://doi.org/10.1002/mc.22642
DOI https://doi.org/10.1002/mc.22642
Keywords TRPA1; Prostate cancer; Tumour microenvironment; Resveratrol; Apoptosis
Publisher URL https://onlinelibrary.wiley.com/doi/abs/10.1002/mc.22642
Copyright Statement ©2018 University of Hull

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