title: Tumor suppression by resistant maltodextrin, Fibersol-2.
abstract: Resistant maltodextrin Fibersol-2 is a soluble and fermentable dietary fiber that is Generally Recognized As Safe (GRAS) in the United States. We tested whether Fibersol-2 contains anti-tumor activity. Human colorectal cancer cell line, HCT116, and its isogenic cells were treated with FIbersol-2. Tumor growth and tumorigenesis were studied in vitro and in vivo. Apoptotic pathway and generation of reactive oxygen species (ROS) were investigated. We discovered that Fibersol-2 significantly inhibits tumor growth of HCT116 cells by inducing apoptosis. Fibersol-2 strongly induces mitochondrial ROS and Bax-dependent cleavage of caspase 3 and 9, which is shown by isogenic HCT116 variants. Fibersol-2 induces phosphorylation of Akt, mTOR in parental HCT116 cells, but not in HCT116 deficient for Bax or p53. It prevents growth of tumor xenograft without any apparent signs of toxicity in vivo. These results identify Fibersol-2 as a mechanism-based dietary supplement agent that could prevent colorectal cancer development.
authors.affiliation: a Department of Cancer Genetics ; Roswell Park Cancer Institute ; Buffalo , NY USA.
authors.forename: Eui Young
authors.initials: EY
authors.lastname: So
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Ouchi
authors.forename: Sara
authors.initials: S
authors.lastname: Cuesta-Sancho
authors.forename: Susan Losee
authors.initials: SL
authors.lastname: Olson
authors.forename: Dirk
authors.initials: D
authors.lastname: Reif
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shimomura
authors.forename: Toru
authors.initials: T
authors.lastname: Ouchi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011134:Polysaccharides / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D011134:Polysaccharides; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C008315:maltodextrin
keywords: BAX, Bcl-2-associated X protein; Fibersol-2; MFI, mean fluorescence intensity; PARP, poly ADP reibose polymerase; ROS, reactive oxygen species; apoptosis; colorectal cancer; mTOR, mammalian target of rapamycin; p53; reactive oxygen species; resistant maltodextrin