Diallyl disulfide (DADS) increases histone acetylation and p21waf1/cip1 expression in human colon tumor cell lines

被引:182
作者
Druesne, N [1 ]
Pagniez, A [1 ]
Mayeur, C [1 ]
Thomas, M [1 ]
Cherbuy, C [1 ]
Duée, PH [1 ]
Martel, P [1 ]
Chaumontet, C [1 ]
机构
[1] INRA, Lab Nutr & Secur Alimentaire, Jouy En Josas, France
关键词
D O I
10.1093/carcin/bgh123
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Diallyl disulfide (DADS) is a naturally occurring organosulfur compound, from garlic, which exerts pleiotropic biological effects. In rodents, DADS inhibits colon chemically induced carcinogenesis. DADS anti-promoting effect may partly result from its ability to inhibit tumoral cell proliferation in vivo and in vitro. As far as DADS may modulate the expression of a subset of genes, we investigated DADS effect on histone acetylation, in two human colon tumor cell lines. Our study demonstrates that in Caco-2 and HT-29 cells treated for 6 h, 200 muM DADS increases histone H3 acetylation (x2 and x1.4, respectively). In Caco-2 cells, we also observed histone H4 hyperacetylation, preferentially at the lysine residues 12 and 16. We explored the effects of DADS and one of its metabolites, allyl mercaptan (AM), on histone deacetylase (HDAC) activity: using nuclear extracts of Caco-2 cells, 200 muM DADS decreased HDAC activity by 29% and AM at the same concentration was more efficient (92% inhibition). We also observed that DADS induced an increase in p21(waf1/cip1) expression, at mRNA and protein levels, in both cell lines. This effect was associated with an accumulation of cells in the G(2) phase of the cell cycle. Our results suggest that in Caco-2 and HT-29 cells, DADS could inhibit cell proliferation through the inhibition of HDAC activity, histone hyperacetylation and increase in p21(waf1/cip1) expression. The present study provides evidence for cellular and molecular responses triggered by DADS that could be linked to its effect on histone acetylation and play a role in its protective properties on colon carcinogenesis.
引用
收藏
页码:1227 / 1236
页数:10
相关论文
共 63 条
[11]   Garlic and cancer: A critical review of the epidemiologic literature [J].
Fleischauer, AT ;
Arab, L .
JOURNAL OF NUTRITION, 2001, 131 (03) :1032S-1040S
[12]   Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin [J].
Furumai, R ;
Komatsu, Y ;
Nishino, N ;
Khochbin, S ;
Yoshida, M ;
Horinouchi, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (01) :87-92
[13]   Transcriptional regulation of the p21(WAF1/ClP1) gene [J].
Gartel, AL ;
Tyner, AL .
EXPERIMENTAL CELL RESEARCH, 1999, 246 (02) :280-289
[14]   In vivo metabolism of diallyl disulphide in the rat:: identification of two new metabolites [J].
Germain, E ;
Auger, J ;
Ginies, C ;
Siess, MH ;
Teyssier, C .
XENOBIOTICA, 2002, 32 (12) :1127-1138
[15]   Expanded lysine acetylation specificity of Gcn5 in native complexes [J].
Grant, PA ;
Eberharter, A ;
John, S ;
Cook, RG ;
Turner, BM ;
Workman, JL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (09) :5895-5900
[16]   Modulation of phase II enzymes by organosulfur compounds from allium vegetables in rat tissues [J].
Guyonnet, D ;
Siess, MH ;
Le Bon, AM ;
Suschetet, M .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1999, 154 (01) :50-58
[17]   Liver subcellular fractions from rats treated by organosulfur compounds from Allium modulate mutagen activation [J].
Guyonnet, D ;
Belloir, C ;
Suschetet, M ;
Siess, MH ;
Le Bon, AM .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2000, 466 (01) :17-26
[18]   Antimutagenic activity of organosulfur compounds from Allium is associated with phase II enzyme induction [J].
Guyonnet, D ;
Belloir, C ;
Suschetet, M ;
Siess, MH ;
Le Bon, AM .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2001, 495 (1-2) :135-145
[19]   Activation of the mouse histone deacetylase 1 gene by cooperative histone phosphorylation and acetylation [J].
Hauser, C ;
Schuettengruber, B ;
Bartl, S ;
Lagger, G ;
Seiser, C .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (22) :7820-7830
[20]   Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemia [J].
He, LZ ;
Tolentino, T ;
Grayson, P ;
Zhong, S ;
Warrell, RP ;
Rifkind, RA ;
Marks, PA ;
Richon, VM ;
Pandolfi, PP .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 108 (09) :1321-1330