Modulation of histone deacetylase activity by dietary isothiocyanates and allyl sulfides: studies with sulforaphane and garlic organosulfur compounds.
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.
Nian
Hui
H
Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331-6512, USA.
Delage
Barbara
B
Ho
Emily
E
Dashwood
Roderick H
RH
D000498:Allyl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005737:Garlic / Q000737:chemistry*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control; D010945:Plants, Edible / Q000737:chemistry; D011485:Protein Binding; D013440:Sulfides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013454:Sulfoxides; D013861:Thiocyanates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D056572:Histone Deacetylase Inhibitors; D017879:Isothiocyanates; D013440:Sulfides; D013454:Sulfoxides; D013861:Thiocyanates; C038491:allyl sulfide; C016766:sulforaphane