Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF).
Mol Carcinog
; 56(8): 1851-1867, 2017 08.
Article
en En
| MEDLINE
| ID: mdl-28277613
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_prostate_cancer
Asunto principal:
Próstata
/
Neoplasias de la Próstata
/
Estilbenos
/
Canales de Calcio
/
Anticarcinógenos
/
Canales de Potencial de Receptor Transitorio
/
Fibroblastos Asociados al Cáncer
/
Proteínas del Tejido Nervioso
/
Antioxidantes
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Mol Carcinog
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
Francia