Dietary folate deficiency blocks prostate cancer progression in the TRAMP model
Menée sur un modèle murin, cette étude évalue l'effet préventif d'une suppression de folates d'origine alimentaire sur le développement du cancer de la prostate
Dietary folate is essential in all tissues to maintain several metabolite pools and cellular proliferation. Prostate cells, due to specific metabolic characteristics, have increased folate demand to support proliferation and prevent genetic and epigenetic damage. Although several studies found that dietary folate interventions can affect colon cancer biology in rodent models, impact on prostate is unknown. The purpose of this study was to determine if dietary folate manipulation, possibly being of primary importance for prostate epithelial cell metabolism, could significantly affect prostate cancer (CaP) progression. Strikingly, mild dietary folate depletion arrested CaP progression in 25/26 transgenic TRAMP mice, where tumorigenesis is prostate specific and characteristically aggressive. The significant effect on CaP growth was characterized by size, grade, proliferation and apoptosis analyses. Folate supplementation had a mild, non significant beneficial effect on grade. In addition, characterization of folate pools (correlated with serum), metabolite pools (polyamines, nucleotides), genetic and epigenetic damage, and expression of key biosynthetic enzymes in prostate tissue revealed interesting correlations with tumor progression. These findings indicate that CaP is highly sensitive to folate manipulation and suggest that antifolates, paired to current therapeutic strategies, might significantly improve treatment of CaP, the most commonly diagnosed cancer in American men.