title: Proteomic analysis of butyrate effects and loss of butyrate sensitivity in HT29 colorectal cancer cells.
abstract: Butyrate, a fermentation product of the large bowel microflora, is potentially protective against the development of colorectal cancer. In vitro, butyrate has been shown to induce apoptosis and inhibit proliferation in numerous cancer cell lines, including colorectal cancer. Although these tumor suppressing properties of butyrate are well-documented in experimental systems, the mechanisms underlying the induction of these effects are not fully understood. Understanding these mechanisms in cancer cells, as well as the pathways involved in a cell's ability to overcome them and progress toward malignancy, is vital to determine therapeutic approaches for disease management. We have developed a colorectal cancer cell line (HT29-BR) that is less responsive to the apoptotic effects of butyrate through sustained exposure of HT29 cells to 5 mM butyrate and have used proteomics to investigate the mechanisms involved in the development of butyrate insensitivity. Proteomic analysis identified a number of cellular processes in HT29 and HT29-BR cells influenced by butyrate including remodeling of the actin cytoskeleton, inhibition of protein biosynthesis and dysregulation of the cell stress response. We describe novel roles for butyrate in the induction of its tumor suppressing effects and outline potential cellular pathways involved in the development of butyrate insensitivity in the HT29-BR cell population.
authors.affiliation: CSIRO Preventative Health Flagship, Australia, CSIRO, Human Nutrition, Adelaide, Australia, CSIRO, Division of Molecular and Health Technologies, Adelaide, Australia.
authors.forename: Kim Y C
authors.initials: KY
authors.lastname: Fung
authors.forename: Tanya
authors.initials: T
authors.lastname: Lewanowitsch
authors.forename: Steven T
authors.initials: ST
authors.lastname: Henderson
authors.forename: Ilka
authors.initials: I
authors.lastname: Priebe
authors.forename: Peter
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Shaun R
authors.initials: SR
authors.lastname: McColl
authors.forename: Trevor
authors.initials: T
authors.lastname: Lockett
authors.forename: Richard
authors.initials: R
authors.lastname: Head
authors.forename: Leah J
authors.initials: LJ
authors.lastname: Cosgrove
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D019073:HT29 Cells; D006801:Humans; D020011:Protective Agents / Q000494:pharmacology*; D020543:Proteome / Q000187:drug effects / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D002087:Butyrates; D020011:Protective Agents; D020543:Proteome