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Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines

Nathalie Druesne1, Anthony Pagniez, Camille Mayeur

  • 1Laboratoire de Nutrition et Securite Alimentaire, INRA, Jouy-en-Josas, France. druesne@jouy.inra.fr

Carcinogenesis
|February 21, 2004
PubMed

Insights

Diallyl disulfide (DADS), a compound found in garlic, inhibits colon cancer cell growth by increasing histone acetylation and p21 expression, while decreasing histone deacetylase (HDAC) activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Nutritional Science

Background:

  • Diallyl disulfide (DADS) is a garlic-derived organosulfur compound with demonstrated anti-cancer properties in rodent models.
  • DADS's anti-promoting effects in colon carcinogenesis may involve the inhibition of tumor cell proliferation.
  • Gene expression modulation by DADS suggests a role in epigenetic modifications like histone acetylation.

Purpose of the Study:

  • To investigate the effect of DADS on histone acetylation in human colon tumor cell lines (Caco-2 and HT-29).
  • To explore the impact of DADS and its metabolite allyl mercaptan (AM) on histone deacetylase (HDAC) activity.
  • To determine the influence of DADS on p21(waf1/cip1) expression and cell cycle progression.

Main Methods:

  • Treatment of Caco-2 and HT-29 cells with 200 microM DADS for 6 hours.
  • Assay of histone H3 and H4 acetylation levels.
  • Measurement of HDAC activity in nuclear extracts using DADS and AM.
  • Analysis of p21(waf1/cip1) mRNA and protein expression via RT-PCR and Western blot.
  • Cell cycle analysis using flow cytometry.

Main Results:

  • DADS significantly increased histone H3 acetylation in both Caco-2 (x2) and HT-29 (x1.4) cells.
  • Histone H4 hyperacetylation was observed in Caco-2 cells, particularly at lysine residues 12 and 16.
  • DADS inhibited HDAC activity by 29%, while AM achieved 92% inhibition.
  • DADS elevated p21(waf1/cip1) expression and induced G2 cell cycle arrest in both cell lines.

Conclusions:

  • DADS may inhibit colon tumor cell proliferation via HDAC inhibition, histone hyperacetylation, and increased p21(waf1/cip1) expression.
  • These epigenetic modifications induced by DADS contribute to its potential protective effects against colon carcinogenesis.
  • The study highlights cellular and molecular mechanisms underlying DADS's chemopreventive properties.

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