title: Combined treatment of Caco-2 cells with butyrate and mesalazine inhibits cell proliferation and reduces Survivin protein level.
abstract: There is epidemiological evidence, that mesalazine can inhibit colon cancer development by affecting proliferation and apoptosis. Several studies suggest that supplementary intake of butyrate may yield to improved efficacy of mesalazine. However, the underlying molecular mechanisms of such interaction remain unknown. This study addressed the combinatory effect of both substances on the growth of Caco-2 cells. Challenging of cells with mesalazine and butyrate provoked a time-dependent decrease in both cell counts and proliferation. Co-treatment with the substances could further intensify these effects. The growth-inhibitory action of mesalazine and butyrate was accompanied by a significant increase in caspase-3 activity, cleavage of PARP and caspase-8, while decreasing the expression of Xiap and Survivin simultaneously. Co-incubation of both substances exaggerated effects on all examined apoptosis-regulatory proteins except for Xiap. Our data demonstrate that co-treatment of mesalazine and butyrate evoked additive effects on inhibition of cell growth and induction of apoptosis in Caco-2 cells.
authors.affiliation: First Department of Medicine-ZAFES, Division of Gastroenterology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. M.Schwab@med.uni-frankfurt.de
authors.forename: Markus
authors.initials: M
authors.lastname: Schwab
authors.forename: Veerle
authors.initials: V
authors.lastname: Reynders
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
authors.forename: Jürgen
authors.initials: J
authors.lastname: Stein
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019804:Mesalamine / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D000077022:Survivin; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C107489:BIRC5 protein, human; D002087:Butyrates; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D019804:Mesalamine; D053148:Caspase 3