Effects of flavonoids on cell proliferation and caspase activation in a human colonic cell line HT29: an SAR study.
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.
Daskiewicz
Jean-Baptiste
JB
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.
Depeint
Flore
F
Viornery
Lionel
L
Bayet
Christine
C
Comte-Sarrazin
Geraldine
G
Comte
Gilles
G
Gee
Jennifer M
JM
Johnson
Ian T
IT
Ndjoko
Karine
K
Hostettmann
Kurt
K
Barron
Denis
D
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
D000970:Antineoplastic Agents; D020536:Enzyme Activators; D047309:Flavones; D005419:Flavonoids; D002599:Chalcone; D020169:Caspases