Estudios científicos
Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells
Abstract:
As inflammation emerges as a risk factor for prostate cancer (PCa), there is potential for chemoprevention by anti-inflammatory agents. Dietary phytochemicals have been shown to have chemopreventive properties which may include anti-inflammatory activities. In this study, we demonstrate a role for mitogen-activated protein kinase phosphatase-5 (MKP5) in mediating anti-inflammatory activities of the phytochemicals curcumin, resveratrol and [6]-gingerol. We utilized the cytokines tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta to increase p38-dependent nuclear factor kappa-B (NFkappaB) activation and expression of pro-inflammatory genes cyclooxygenase-2 (COX-2), IL-6 and IL-8 in normal prostatic epithelial cells. MKP5 over-expression decreased cytokine-induced NFkappaB activation, COX-2, IL-6 and IL-8 in normal prostatic epithelial cells, suggesting potent anti-inflammatory activity of MKP5. Pretreatment of cells with a p38 inhibitor mimicked the results observed with MKP5 over-expression, further implicating p38 inhibition as the main activity of MKP5. Curcumin, the phytochemical found in turmeric, up-regulated MKP5, subsequently decreasing cytokine-induced p38-dependent pro-inflammatory changes in normal prostatic epithelial cells. Resveratrol and [6]-gingerol, phytochemicals present in red wine and ginger, respectively, also up-regulated MKP5 in normal prostate epithelial cells. Moreover, we found that PCa cell lines DU 145, PC-3, LNCaP and LAPC-4 retained the ability to up-regulate MKP5 following curcumin, resveratrol and [6]-gingerol exposure, suggesting utility of these phytochemicals in PCa treatment. In summary, our findings show direct anti-inflammatory activity of MKP5 in prostate cells and suggest that up-regulation of MKP5 by phytochemicals may contribute to their chemopreventive actions by decreasing prostatic inflammation.
Comentarios divulgativos:
La inflamación se presenta como un factor de riesgo para el cáncer de próstata (PCa), existe la posibilidad de la quimioprevención por agentes anti-inflamatorios. Los fitoquímicos dietéticos han demostrado tener propiedades quimiopreventivas que pueden incluir actividades anti-inflamatorias. En este estudio se demuestra que los mitógenos activados por la proteína quinasa fosfatasa-5 (MKP5) en la mediación de las actividades anti-inflamatoria del resveratrol] Hicimos uso del factor de necrosis tumoral citoquinas-alfa (TNFa) y la interleuquina (IL)-1beta para aumentar la activación p38 dependiente del factor nuclear kappa-B (NFkappaB) y la expresión de genes pro-inflamatorios: ciclooxigenasa-2 (COX-2), IL -6 e IL-8 en células epiteliales normales de próstata. MKP5 .El pretratamiento de las células con un inhibidor de p38 imitaba los resultados observados con MKP5 sobre-expresión, implicando más p38 como la inhibición de la actividad principal de MKP5. Por otra parte, encontramos que las líneas de células DU CAP 145, PC-3, LNCaP y LAPC 4-mantienen la capacidad de regular MKP5 lo que sugiere la utilidad de estos fitoquímicos en el tratamiento del CaP. En resumen, nuestros hallazgos muestran actividad anti-inflamatoria de MKP5 en células de la próstata y sugieren que la regulación positiva de MKP5 por fitoquímicos pueden contribuir a sus acciones quimiopreventivos al disminuir la inflamación de próstata.
