Dietary sulforaphane, a histone deacetylase inhibitor for cancer prevention.
The reversible acetylation of histones is an important mechanism of gene regulation. During prostate cancer progression, specific modifications in acetylation patterns on histones are apparent. Targeting the epigenome, including the use of histone deacetylase (HDAC) inhibitors, is a novel strategy for cancer chemoprevention. Recently, drugs classified as HDAC inhibitors have shown promise in cancer clinical trials. We have previously found that sulforaphane (SFN), a compound found in cruciferous vegetables, inhibits HDAC activity in human colorectal and prostate cancer cells. Based on the similarity of SFN metabolites and other phytochemicals to known HDAC inhibitors, we previously demonstrated that sulforaphane acted as an HDAC inhibitor in the prostate, causing enhanced histone acetylation, derepression of P21 and Bax, and induction of cell cycle arrest/apoptosis, leading to cancer prevention. The ability of SFN to target aberrant acetylation patterns, in addition to effects on phase 2 enzymes, may make it an effective chemoprevention agent. These studies are important because of the potential to qualify or change recommendations for high-risk prostate cancer patients and thereby increase their survival through simple dietary choices incorporating easily accessible foods into their diets. These studies also will provide a strong scientific foundation for future large-scale human clinical intervention studies.
Ho
Emily
E
Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis OR 97331, USA. emily.ho@oregonstate.edu
Clarke
John D
JD
Dashwood
Roderick H
RH
D000107:Acetylation; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001682:Biological Availability; D001937:Brassica; D004032:Diet; D019587:Dietary Supplements; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005786:Gene Expression Regulation; D042822:Genomic Instability; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates; D007583:Jejunum / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D013454:Sulfoxides; D013861:Thiocyanates / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D014158:Transcription, Genetic
D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D006655:Histone Deacetylases; C016766:sulforaphane