title: Chemoprevention of esophageal cancer with black raspberries, their component anthocyanins, and a major anthocyanin metabolite, protocatechuic acid.
abstract: Diets containing either freeze-dried black raspberries (BRBs) or their polyphenolic anthocyanins (ACs) have been shown to inhibit the development of N-nitrosomethylbenzylamine (NMBA)-induced esophageal cancer in rats. The present study was conducted to determine whether PCA, a major microbial metabolite of black raspberry (BRB) ACs, also prevents NMBA-induced esophageal cancer in rats. F344 rats were injected with NMBA three times a week for 5 weeks and then fed control or experimental diets containing 6.1% BRBs, an anthocyanin (AC)-enriched fraction derived from BRBs, or protocatechuic acid (PCA). Animals were exsanguinated at weeks 15, 25, and 35 to quantify the development of preneoplastic lesions and tumors in the esophagus, and to relate this to the expression of inflammatory biomarkers. At weeks 15 and 25, all experimental diets were equally effective in reducing NMBA-induced esophageal tumorigenesis, as well as in reducing the expression of pentraxin-3 (PTX3), a cytokine produced by peripheral blood mononuclear cells in response to interleukin (IL)-1β and TNF-α. All experimental diets were also active at reducing tumorigenesis at week 35; however, the BRB diet was significantly more effective than the AC and PCA diets. Furthermore, all experimental diets inhibited inflammation in the esophagus via reducing biomarker (COX-2, iNOS, p-NF-κB, and sEH) and cytokine (PTX3) expression. Overall, our data suggest that BRBs, their component ACs, and PCA inhibit NMBA-induced esophageal tumorigenesis, at least in part, by their inhibitory effects on genes associated with inflammation.
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Peiffer
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Noah P
authors.initials: NP
authors.lastname: Zimmerman
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Benjamin W S
authors.initials: BW
authors.lastname: Ransom
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Carmella
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Chieh-Ti
authors.initials: CT
authors.lastname: Kuo
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Jibran
authors.initials: J
authors.lastname: Siddiqui
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Jo-Hsin
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Oshima
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Huang
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Hecht
authors.affiliation: Authors' Affiliations: Departments of Medicine, Pathology, and Obstetrics and Gynecology, Medical College of Wisconsin Cancer Center; Agro BioSciences Inc., Milwaukee, Wisconsin; and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota gstoner@mcw.edu.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stoner
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods; D004035:Diet Therapy; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives; D004938:Esophageal Neoplasms / Q000517:prevention & control*; D005638:Fruit; D062385:Hydroxybenzoates / Q000302:isolation & purification / Q000627:therapeutic use*; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D011916:Rats, Inbred F344; D065856:Rubus / Q000737:chemistry
chemical_list: D000872:Anthocyanins; D016588:Anticarcinogenic Agents; D062385:Hydroxybenzoates; D010936:Plant Extracts; C009091:protocatechuic acid; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine