title: Effects of a grape-supplemented diet on proliferation and Wnt signaling in the colonic mucosa are greatest for those over age 50 and with high arginine consumption.
abstract: A diet rich in fruits and vegetables, and a grape-derived compound, resveratrol, have been linked to a reduced incidence of colon cancer. In vitro and in vivo, resveratrol suppresses Wnt signaling, a pathway constitutively activated in over 85 % of colon cancers.Thirty participants were placed on a low resveratrol diet and subsequently allocated to one of three groups ingesting 1/3-to-1 lb (0.15-0.45 kg) of grapes per day for 2 weeks. Dietary information was collected via 24-h recall. Colon biopsies for biomarker analysis were obtained pre- and post-grape and evaluated for the expression of Wnt pathway target genes and for markers of proliferation by RT-PCR and immunohistochemistry.Participants lost an average of 2 · 6 lb (1.2 kg, p = 0 · 0018) during the period of grape ingestion. The expression of CyclinD1 (p < 0 · 01), AXIN2, CD133 (p = 0 · 02) and Ki67 (p = 0 · 002) were all reduced after grape ingestion. Individuals over 50 years of age and those with high dietary arginine consumption had increased basal expression of CyclinD1, AXIN2, cMYC and CD133 (p value range 0 · 04 to <0 · 001) that, following grape ingestion, were reduced to levels seen in younger participants.The reduction in Wnt signaling and mucosal proliferation seen following short-term ingestion of 1/3-1 lb (0.15-0.45 kg) of grapes per day may reduce the risk of mutational events that can facilitate colon carcinogenesis. The potential benefit is most marked for high-risk older individuals and individuals whose diet is high in arginine intake. Dietary grape supplementation may play a role in colon cancer prevention for high-risk individuals.
authors.affiliation: Division of Hematology & Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustav L. Levy Place, Box 1128, New York, NY, 10029, USA. Randall.holcombe@mssm.edu.
authors.forename: Randall F
authors.initials: RF
authors.lastname: Holcombe
authors.affiliation: University of California, Irvine, USA.
authors.forename: Micaela
authors.initials: M
authors.lastname: Martinez
authors.affiliation: Division of Hematology & Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustav L. Levy Place, Box 1128, New York, NY, 10029, USA.
authors.forename: Kestutis
authors.initials: K
authors.lastname: Planutis
authors.affiliation: Division of Hematology & Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustav L. Levy Place, Box 1128, New York, NY, 10029, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Planutiene
mesh_terms: D000071916:AC133 Antigen; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000008:administration & dosage*; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000517:prevention & control; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004032:Diet; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D011939:Mental Recall; D008875:Middle Aged; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage; D027843:Vitis / Q000737:chemistry*; D060449:Wnt Signaling Pathway; D055815:Young Adult
chemical_list: D000071916:AC133 Antigen; C491761:AXIN2 protein, human; D015703:Antigens, CD; D060466:Axin Protein; D015415:Biomarkers; C530104:CCND1 protein, human; D006023:Glycoproteins; C489427:MYC protein, human; C000606023:PROM1 protein, human; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc; D013267:Stilbenes; D019938:Cyclin D1; D001120:Arginine; D000077185:Resveratrol