Diallyl disulfide increases CDKN1A promoter-associated histone acetylation in human colon tumor cell lines.
Diallyl disulfide (DADS) is an organosulfur compound from garlic, which inhibits colon tumor cell proliferation. In a previous study, we have shown that in Caco-2 and HT-29 cells DADS (200 microM) increases global histone acetylation, CDKN1A mRNA, and p21(waf1) protein levels and induces G2/M cell cycle arrest. These results suggested that DADS could inhibit cell proliferation through at least in part a transcriptional activation of CDKN1A expression involving histone acetylation. In this study, using chromatin immunoprecipitation assays, we demonstrate that in Caco-2 and HT-29 cells histone H4 and/or H3 acetylation is increased within CDKN1A promoter after 3 and 6 h treatments with DADS. These results strongly suggest that histone acetylation, a molecular mechanism implicated in the regulation of gene expression, could account for the induction of CDKN1A expression and the antiproliferating effects of DADS in colon tumor cells.
Druesne-Pecollo
Nathalie
N
Laboratoire de Nutrition et Sécurité Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France. Nathalie.Pecollo@jouy.inra.fr
Pagniez
Anthony
A
Thomas
Muriel
M
Cherbuy
Claire
C
Duée
Pierre-Henri
PH
Martel
Paule
P
Chaumontet
Catherine
C
D000107:Acetylation / Q000187:drug effects; D000498:Allyl Compounds / Q000494:pharmacology*; D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004220:Disulfides / Q000494:pharmacology*; D019073:HT29 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology*
D000498:Allyl Compounds; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004220:Disulfides; D006657:Histones; C028009:diallyl disulfide