title: Improvement of replication fidelity by certain mesalazine derivatives.
abstract: Epidemiological evidence on the chemopreventive activity of mesalazine against             colitis-associated cancer has accumulated in recent years. Together with the variety             of mesalazine molecular antitumor effects this has prompted the development of             novel mesalazine derivatives. The objective of this study was to test five novel             derivatives (compounds 2-14, 2-17, 2-28, 2-34L, 2-39) for their effect on cell             proliferation, their capability to scavenge superoxide anions, to induce a cell             cycle arrest and to improve replication fidelity in cultured colorectal cells.             Compound 2-14 was identified as the strongest inhibitor of cell proliferation             and functioned as a potent superoxide scavenger, as did 2-17 and 2-34L. 2-14 induced             a G2/M-arrest in HCT116 and a G0/G1-arrest in HT29 cells. 2-17 caused a G0/G1-arrest             and 2-34L a G2/M-arrest in HT29 cells. 2-17 and 2-34L reduced mutation rates at             a (CA)13 repeat in a dose-dependent fashion. These data suggest that certain mesalazine             derivatives share important antitumor effects. From this experimental profile             compounds 2-17 and 2-34L both improve replication fidelity, which is biologically             relevant not only for colitis-associated cancer but also potentially for individuals             with hereditary non-polyposis colorectal cancer.
authors.affiliation: Christian Doppler Laboratory for Molecular Cancer Chemoprevention,                     Medical University of Vienna, Vienna, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Honeder
authors.forename: Christoph
authors.initials: C
authors.lastname: Campregher
authors.forename: Bettina
authors.initials: B
authors.lastname: Zens
authors.forename: Theresa
authors.initials: T
authors.lastname: Scharl
authors.forename: Christoph
authors.initials: C
authors.lastname: Gasche
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D019804:Mesalamine / Q000494:pharmacology*; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016588:Anticarcinogenic Agents; D018797:Cell Cycle Proteins; D016166:Free Radical Scavengers; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D013481:Superoxides; D019804:Mesalamine; D011494:Protein Kinases; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D000070957:MutL Protein Homolog 1