Modulation of histone deacetylase activity by dietary isothiocyanates and allyl sulfides: Studies with sulforaphane and garlic organosulfur compounds
- 5 February 2009
- journal article
- review article
- Published by Wiley in Environmental and Molecular Mutagenesis
- Vol. 50 (3), 213-221
- https://doi.org/10.1002/em.20454
Abstract
Histone deacetylase (HDAC) inhibitors reactivate epigenetically‐silenced genes in cancer cells, triggering cell cycle arrest and apoptosis. Recent evidence suggests that dietary constituents can act as HDAC inhibitors, such as the isothiocyanates found in cruciferous vegetables and the allyl compounds present in garlic. Broccoli sprouts are a rich source of sulforaphane (SFN), an isothiocyanate that is metabolized via the mercapturic acid pathway and inhibits HDAC activity in human colon, prostate, and breast cancer cells. In mouse preclinical models, SFN inhibited HDAC activity and induced histone hyperacetylation coincident with tumor suppression. Inhibition of HDAC activity also was observed in circulating peripheral blood mononuclear cells obtained from people who consumed a single serving of broccoli sprouts. Garlic organosulfur compounds can be metabolized to allyl mercaptan (AM), a competitive HDAC inhibitor that induced rapid and sustained histone hyperacetylation in human colon cancer cells. Inhibition of HDAC activity by AM was associated with increased histone acetylation and Sp3 transcription factor binding to the promoter region of the P21WAF1 gene, resulting in elevated p21 protein expression and cell cycle arrest. Collectively, the results from these studies, and others reviewed herein, provide new insights into the relationships between reversible histone modifications, diet, and cancer chemoprevention. Environ. Mol. Mutagen., 2009.This publication has 93 references indexed in Scilit:
- Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compoundsCancer Letters, 2008
- Multi-targeted prevention of cancer by sulforaphaneCancer Letters, 2008
- Dietary Manipulation of Histone Structure and FunctionAnnual Review of Nutrition, 2008
- Allyl mercaptan, a garlic-derived organosulfur compound, inhibits histone deacetylase and enhances Sp3 binding on the P21WAF1 promoterCarcinogenesis: Integrative Cancer Research, 2008
- Alkenyl group is responsible for the disruption of microtubule network formation in human colon cancer cell line HT-29 cellsCarcinogenesis: Integrative Cancer Research, 2008
- Dietary histone deacetylase inhibitors: From cells to mice to manSeminars in Cancer Biology, 2007
- Clinical effectiveness of garlic (Allium sativum)Molecular Nutrition & Food Research, 2007
- Molecular basis for chemoprevention by sulforaphane: a comprehensive reviewCellular and Molecular Life Sciences, 2007
- Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basisPharmacological Research, 2007
- Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancerNature Genetics, 2005