title: Effects of flavonoids on cell proliferation and caspase activation in a human colonic cell line HT29: an SAR study.
abstract: A library of 42 natural and synthetic flavonoids has been screened for their effect on cell proliferation and apoptosis in a human colonic cell line (HT-29). Examples of different classes of flavonoids have been screened, and the effects of hydroxylation, methoxylation and/or C-alkylation at various positions in the A- and B-rings have been assessed. Flavones and flavonols possess greater antiproliferative activity than chalcones and flavanones. With respect to structural modification of flavonoids, C-isoprenylation was by far the most effective, with substitution at the 8-position and longer chains, such as geranyl giving the best results. Finally, most compounds that significantly reduced cell survival also increased caspase activity, suggesting that at least part of their antiproliferative activity might be attributable to an apoptotic response.
authors.affiliation: Laboratoire des Produits Naturels, CNRS-UMR 5013, UFR de Chimie-Biochimie, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Daskiewicz
authors.forename: Flore
authors.initials: F
authors.lastname: Depeint
authors.forename: Lionel
authors.initials: L
authors.lastname: Viornery
authors.forename: Christine
authors.initials: C
authors.lastname: Bayet
authors.forename: Geraldine
authors.initials: G
authors.lastname: Comte-Sarrazin
authors.forename: Gilles
authors.initials: G
authors.lastname: Comte
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Gee
authors.forename: Ian T
authors.initials: IT
authors.lastname: Johnson
authors.forename: Karine
authors.initials: K
authors.lastname: Ndjoko
authors.forename: Kurt
authors.initials: K
authors.lastname: Hostettmann
authors.forename: Denis
authors.initials: D
authors.lastname: Barron
mesh_terms: D000478:Alkylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003110:Colonic Neoplasms; D020536:Enzyme Activators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006900:Hydroxylation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D020536:Enzyme Activators; D047309:Flavones; D005419:Flavonoids; D002599:Chalcone; D020169:Caspases