title: Beneficial Regulation of Metabolic Profiles by Black Raspberries in Human Colorectal Cancer Patients.
abstract: Dietary intervention of freeze-dried black raspberries (BRBs) in a group of human colorectal cancer patients has demonstrated beneficial effects, including proapoptosis, antiproliferation, and antiangiogenesis. The aim of this study was to investigate BRB-mediated metabolite changes from this same cohort of patients. Twenty-eight colorectal cancer patients were given 60 g BRB powder daily for 1 to 9 weeks. Urine and plasma specimens were collected before and after BRB intervention. A mass spectrometry-based nontargeted metabolomic analysis was conducted on each specimen. A total of more than 400 metabolites were annotated in each specimen. Of these 34 and 6 metabolites were significantly changed by BRBs in urine and plasma, respectively. Increased levels of 4-methylcatechol sulfate in both post-BRB urine and post-BRB plasma were significantly correlated with a higher level of apoptotic marker (TUNEL) in post-BRB tumors. One tricarboxylic acid (TCA) cycle metabolites, cis-aconitate, was increased in post-BRB urine. Furthermore, BRB-derived polyphenols were absorbed and metabolized to various benzoate species, which were significantly increased in post-BRB specimens. Increased benzoate levels were positively correlated with enhanced levels of amino acid metabolite. These results suggest that BRBs induce significant metabolic changes and affect energy generating pathways.This study supports the hypothesis that BRBs might be beneficial to colorectal cancer patients through the regulation of multiple metabolites.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Pan
authors.initials: P
authors.lastname: Pan
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Chad W
authors.initials: CW
authors.lastname: Skaer
authors.affiliation: Clinical Research and Development, Metabolon Inc., Durham, North Carolina.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Stirdivant
authors.affiliation: Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, Maryland.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Young
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stoner
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: John F
authors.initials: JF
authors.lastname: Lechner
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: Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. liswang@mcw.edu.
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D002853:Chromatography, Liquid; D015179:Colorectal Neoplasms / Q000097:blood* / Q000178:diet therapy / Q000652:urine*; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D055442:Metabolome / Q000187:drug effects*; D065856:Rubus / Q000737:chemistry*; D053719:Tandem Mass Spectrometry