title: Dietary folate deficiency blocks prostate cancer progression in the TRAMP model.
abstract: 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 have found that dietary folate interventions can affect colon cancer biology in rodent models, its impact on prostate is unknown. The purpose of this study was to determine whether dietary folate manipulation, possibly being of primary importance for prostate epithelial cell metabolism, could significantly affect prostate cancer progression. Strikingly, mild dietary folate depletion arrested prostate cancer progression in 25 of 26 transgenic adenoma of the mouse prostate (TRAMP) mice, in which tumorigenesis is prostate-specific and characteristically aggressive. The significant effect on prostate cancer growth was characterized by size, grade, proliferation, and apoptosis analyses. Folate supplementation had a mild, nonsignificant, beneficial effect on grade. In addition, characterization of folate pools (correlated with serum), metabolite pools (polyamines and nucleotides), genetic and epigenetic damage, and expression of key biosynthetic enzymes in prostate tissue revealed interesting correlations with tumor progression. These findings indicate that prostate cancer is highly sensitive to folate manipulation and suggest that antifolates, paired with current therapeutic strategies, might significantly improve treatment of prostate cancer, the most commonly diagnosed cancer in American men.
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Elm & Carlton streets, BLSC L3-314, Buffalo, NY 14263, USA.
authors.forename: Gaia
authors.initials: G
authors.lastname: Bistulfi
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Foster
authors.forename: Ellen
authors.initials: E
authors.lastname: Karasik
authors.forename: Bryan
authors.initials: B
authors.lastname: Gillard
authors.forename: Jeff
authors.initials: J
authors.lastname: Miecznikowski
authors.forename: Vineet K
authors.initials: VK
authors.lastname: Dhiman
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Smiraglia
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004032:Diet; D004195:Disease Models, Animal; D018450:Disease Progression; D005492:Folic Acid / Q000378:metabolism*; D005494:Folic Acid Deficiency; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D005492:Folic Acid