title: Dietary Consumption of Black Raspberries or Their Anthocyanin Constituents Alters Innate Immune Cell Trafficking in Esophageal Cancer.
abstract: Freeze-dried black raspberries (BRB), their component anthocyanins (AC), and a metabolite of BRB ACs, protocatechuic acid (PCA), inhibit the development of esophageal cancer in rats induced by the carcinogen, N-nitrosomethylbenzylamine (NMBA). All three components reduce inflammation in the esophagus and in plasma. The present study determined the relation of changes in inflammatory markers to infiltration of innate immune cells into NMBA-treated esophagus. Rats were injected with NMBA (0.35 mg/kg) for 5 weeks while on control diet. Following NMBA treatment, rats were fed diets containing 6.1% BRB powder, an AC-rich fraction of BRBs (3.8 μmol/g), or 500 ppm PCA. At weeks 15, 25, and 35, inflammatory biomarker expression in the plasma and esophagus was quantified, and infiltration of immune cells in the esophagus was examined. At all three time points, BRB, AC, and PCA similarly affected cytokine production in the esophagus and plasma of NMBA-treated rats, relative to the NMBA-only control. These included decreased expression of the proinflammatory cytokine IL1β and increased expression of the anti-inflammatory cytokine IL10. Moreover, all three diets also increased the expression of IL12, a cytokine that activates both cytolytic natural killer and CD8(+) T cells. In addition, the three diets also decreased infiltration of both macrophages and neutrophils into the esophagus. Overall, our results suggest that another mechanism by which BRBs, ACs, and PCA inhibit NMBA-induced esophageal tumorigenesis is by altering cytokine expression and innate immune cell trafficking into tumor tissues.
authors.affiliation: Department of Medicine, Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Peiffer
authors.affiliation: Department of Medicine, Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin.
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Agro BioSciences Inc., Milwaukee, Wisconsin.
authors.forename: Noah P
authors.initials: NP
authors.lastname: Zimmerman
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Benjamin W S
authors.initials: BW
authors.lastname: Ransom
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Carmella
authors.affiliation: Department of Medicine, Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin.
authors.forename: Chieh-Ti
authors.initials: CT
authors.lastname: Kuo
authors.affiliation: Department of Medicine, Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin.
authors.forename: Jo-Hsin
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Oshima
authors.affiliation: Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Huang
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Hecht
authors.affiliation: Department of Medicine, Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin. gstoner@mcw.edu.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stoner
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000178:diet therapy*; D004032:Diet; D004354:Drug Screening Assays, Antitumor; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000178:diet therapy*; D004947:Esophagus / Q000276:immunology / Q000473:pathology; D005638:Fruit / Q000737:chemistry; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D009389:Neovascularization, Pathologic / Q000178:diet therapy / Q000276:immunology; D020556:Neutrophil Infiltration; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D065856:Rubus / Q000737:chemistry
chemical_list: D000872:Anthocyanins; D000972:Antineoplastic Agents, Phytogenic