El té verde y el vino inhiben el crecimiento del cancer de prostata vía inhibición de SphK1/S1P

Foro general ciencia, medicina, nutrición, salud pública, política

Moderador: Fisio

El té verde y el vino inhiben el crecimiento del cancer de prostata vía inhibición de SphK1/S1P

Notapor Fisio » Sab, 31 May 2014, 01:42


The sphingosine kinase-1 survival pathway is a molecular target for the tumor-suppressive tea and wine polyphenols in prostate cancer

Abstract

The sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway has been associated with cancer promotion and progression and resistance to treatments in a number of cancers, including prostate adenocarcinoma. Here we provide the first evidence that dietary agents, namely, epigallocatechin gallate (EGCg, IC50≈75 μM), resveratrol (IC50≈40 μM), or a mixture of polyphenols from green tea [polyphenon E (PPE), IC50≈70 μM] or grapevine extract (vineatrol, IC50≈30 μM), impede prostate cancer cell growth in vitro and in vivo by inhibiting the SphK1/S1P pathway. We establish that SphK1 is a downstream effector of the ERK/phospholipase D (PLD) pathway, which is inhibited by green tea and wine polyphenols. Enforced expression of SphK1 impaired the ability of green tea and wine polyphenols, as well as pharmacological inhibitors of PLD and ERK activities, to induce apoptosis in PC-3 and C4-2B cells. The therapeutic efficacy of these polyphenols on tumor growth and the SphK1/S1P pathway were confirmed in animals using a heterotopic PC-3 tumor in place model. PC-3/SphK1 cells implanted in animals developed larger tumors and resistance to treatment with polyphenols. Furthermore, using an orthotopic PC-3/GFP model, the chemopreventive effect of an EGCg or PPE diet was associated with SphK1 inhibition, a decrease in primary tumor volume, and occurrence and number of metastases. These results provide the first demonstration that the prosurvival, antiapoptotic SphK1/S1P pathway represents a target of dietary green tea and wine polyphenols in cancer.—Brizuela, L., Dayon, A., Doumerc, N., Ader, I., Golzio, M., Izard, J.-C., Hara, Y., Malavaud, B., Cuvillier, O. The sphingosine kinase-1 survival pathway is a molecular target for the tumor-suppressive tea and wine polyphenols in prostate cancer.


http://www.fasebj.org/content/24/10/3882
Avatar de Usuario
Fisio
Administrador del Sitio
 
Mensajes: 6124
Registrado: Dom, 01 Sep 2013, 14:18

Volver a Muscleblog

¿Quién está conectado?

Usuarios navegando por este Foro: No hay usuarios registrados visitando el Foro y 4 invitados