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Published on: May 14, 2016
Diallyl disulfide increases CDKN1A promoter-associated histone acetylation in human colon tumor cell lines
Nathalie Druesne-Pecollo1, Anthony Pagniez, Muriel Thomas
1Laboratoire de Nutrition et Sécurité Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France. Nathalie.Pecollo@jouy.inra.fr
Abstract:
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.
Insights
Diallyl disulfide (DADS), a garlic compound, inhibits colon tumor cell growth by increasing histone acetylation. This epigenetic modification activates CDKN1A gene expression, leading to cell cycle arrest and reduced proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Diallyl disulfide (DADS) is a garlic-derived organosulfur compound with demonstrated anti-proliferative effects on colon tumor cells.
- Previous research indicated DADS increases histone acetylation and CDKN1A expression, suggesting a role in cell cycle arrest.
Purpose of the Study:
- To investigate the direct effect of DADS on histone acetylation within the CDKN1A promoter in colon cancer cells.
- To elucidate the epigenetic mechanisms underlying DADS-induced inhibition of colon tumor cell proliferation.
Main Methods:
- Chromatin immunoprecipitation (ChIP) assays were performed on Caco-2 and HT-29 colon cancer cell lines.
- Cells were treated with DADS (200 microM) for 3 and 6 hours.
- Analysis focused on histone H3 and H4 acetylation levels at the CDKN1A promoter region.
Main Results:
- DADS treatment significantly increased histone H4 and/or H3 acetylation at the CDKN1A promoter in both cell lines.
- The observed acetylation changes occurred within 3 to 6 hours of DADS exposure.
- These findings correlate with previously observed increases in CDKN1A mRNA and p21(waf1) protein.
Conclusions:
- Histone acetylation of the CDKN1A promoter is a key mechanism by which DADS exerts its anti-proliferative effects in colon tumor cells.
- Epigenetic regulation via histone acetylation plays a crucial role in DADS-mediated cancer chemoprevention.
- DADS represents a potential therapeutic agent for colon cancer, acting through modulation of gene expression.
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