title: Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic cells.
abstract: Apple procyanidins have chemopreventive properties in a model of colon cancer, they affect intracellular signalling pathways, and trigger apoptosis in a human adenocarcinoma-derived metastatic cell line (SW620). In the present study we investigated relationships between procyanidin-induced alterations in polyamine metabolism and apoptotic effects. Apple procyanidins diminish the activities of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, key enzymes of polyamine biosynthesis, and they induce spermidine/spermine N(1)-acetyltransferase, which initiates retroconversion of poly-amines. As a consequence of the enzymatic changes polyamine concentrations are diminished, and N(1)-acetyl-polyamines accumulate in SW620 cells. In contrast with expectations MDL 72527, an inactivator of polyamine oxidase (PAO), improved the anti-proliferative effect of procyanidins, and caused an increase of the proportion of apoptotic cells, although it prevented the formation of hydrogen peroxide and 3-acetamidopropanal, the cytotoxic products of PAO-catalysed degradation of N(1)-acetylspermidine and N1-acetylspermine. Addition of 500 microM N1-acetylspermidine to the culture medium in the presence of procyanidins mimicked the effect of MDL 72527. Therefore we presume that the enhanced procyanidin-triggered apoptosis by MDL 72527 is mediated by the accumulation of N(1)-acetyl-polyamines. The observation that apple procyanidins enhance polyamine catabolism and reduce polyamine biosynthesis activity similar to known inducers of SSAT, without sharing their toxicity, and the potentiation of these effects by low concentrations of MDL 72527 suggests apple procyanidins for chemopreventive and therapeutic interventions.
authors.affiliation: Université Louis-Pasteur EA3430, Faculty of Medicine, INSERM U682, Laboratory of Nutritional Cancer Prevention, IRCAD, Strasbourg, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Gossé
authors.forename: Stamatiki
authors.initials: S
authors.lastname: Roussi
authors.forename: Sylvain
authors.initials: S
authors.lastname: Guyot
authors.forename: Angèle
authors.initials: A
authors.lastname: Schoenfelder
authors.forename: André
authors.initials: A
authors.lastname: Mann
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bergerat
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Seiler
authors.forename: Francis
authors.initials: F
authors.lastname: Raul
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004357:Drug Synergism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D027845:Malus / Q000378:metabolism*; D009362:Neoplasm Metastasis; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000494:pharmacology*; D011073:Polyamines / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D011700:Putrescine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000097667:Polyamine Oxidase
chemical_list: D000970:Antineoplastic Agents; D044946:Biflavonoids; D002392:Catechin; D006861:Hydrogen Peroxide; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D044945:Proanthocyanidins; D011700:Putrescine; D000097667:Polyamine Oxidase; C044445:MDL 72527; C017674:procyanidin