Estudios científicos

Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols


The cancer preventive properties of grape products such as red wine have been attributed to polyphenols enriched in red wine. However, much of the studies on cancer preventive mechanisms of grape polyphenols have been conducted with individual compounds at concentrations too high to be achieved via dietary consumption. We recently reported that combined grape polyphenols at physiologically relevant concentrations are more effective than individual compounds at inhibition of ERalpha(-), ERbeta(+) MDA-MB-231 breast cancer cell proliferation, cell cycle progression, and primary mammary tumor growth (Schlachterman et al., Transl Oncol 1:19-27, 2008). Herein, we show that combined grape polyphenols induce apoptosis and are more effective than individual resveratrol, quercetin, or catechin at inhibition of cell proliferation, cell cycle progression, and cell migration in the highly metastatic ER (-) MDA-MB-435 cell line. The combined effect of dietary grape polyphenols (5 mg/kg each resveratrol, quercetin, and catechin) was tested on progression of mammary tumors in nude mice created from green fluorescent protein-tagged MDA-MB-435 bone metastatic variant. Fluorescence image analysis of primary tumor growth demonstrated a statistically significant decrease in tumor area by dietary grape polyphenols. Molecular analysis of excised tumors demonstrated that reduced mammary tumor growth may be due to upregulation of FOXO1 (forkhead box O1) and NFKBIA (IkappaBalpha), thus activating apoptosis and potentially inhibiting NfkappaB (nuclear factor kappaB) activity. Image analysis of distant organs for metastases demonstrated that grape polyphenols reduced metastasis especially to liver and bone. Overall, these results indicate that combined dietary grape polyphenols are effective at inhibition of mammary tumor growth and site-specific metastasis.

Comentarios divulgativos:

Las propiedades preventivas frente al cáncer de productos como el vino tinto han sido atribuidas a los polifenoles presentes en dicho vino tinto. Sin embargo muchos de los estudios centrados en las propiedades quimiopreventivas se han realizado con concentraciones mayores de las suministradas en la dieta. En recientes estudios estos investigadores han demostrado que polifenoles convinados de la uva a concentraciones fisiológicas son más efectivos que individualmente en la inhibición de la proliferación de células de cáncer de pecho ERalpha(-), ERbeta(+) MDA-MB-231 así como en la progresión del ciclo celular y en el crecimiento primario de tumores de mama. En este estudio se demuestra que la combinación de polifenoles de la uva inducen la apoptosis y son más efectivos que el resveratrol y la quecertina individualmente en la línea celular ER (-) MDA-MB-435. Los resultados indican que una combinación de polifenoles de la uva en la dieta es efectivo en la inhibición del crecimiento del tumor de mama.