Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apcmin mice
| Autor: | Roderick H. Dashwood, W. Mohaiza Dashwood, Melinda C. Myzak, Gayle A. Orner, Emily Ho |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
Genes APC Administration Oral medicine.disease_cause Biochemistry Article Histone H4 Histones Histone H3 chemistry.chemical_compound Mice Isothiocyanates Intestinal Neoplasms Genetics medicine Animals Single-Blind Method Intestinal Mucosa Molecular Biology Caspase Mice Knockout biology Intestinal Polyps Acetylation Molecular biology Chromatin Histone Deacetylase Inhibitors Mice Inbred C57BL Histone Cell Transformation Neoplastic chemistry Sulfoxides biology.protein Histone deacetylase Drug Screening Assays Antitumor Carcinogenesis Protein Processing Post-Translational Thiocyanates Biotechnology Sulforaphane |
| Popis: | Sulforaphane (SFN) is an isothiocyanate from broccoli that induces phase 2 detoxification enzymes. We recently reported that SFN acts as a histone deacetylase (HDAC) inhibitor in human colon cancer cells in vitro, and the present study sought to extend these findings in vivo. In mice treated with a single oral dose of 10 mumol SFN, there was significant inhibition of HDAC activity in the colonic mucosa after 6 h, and immunoblots revealed a concomitant increase in acetylated histones H3 and H4, which returned to control levels by 48 h. Longer-term treatment with SFN in the diet resulted in levels of acetylated histones and p21(WAF1) in the ileum, colon, prostate, and peripheral blood mononuclear cells that were elevated compared with controls. Consistent with these findings, SFN suppressed tumor development in Apc(min) mice, and there was an increase in acetylated histones in the polyps, including acetylated histones specifically associated with the promoter region of the P21 and bax genes. These results provide the first evidence for HDAC inhibition by SFN in vivo and imply that such a mechanism might contribute to the cancer chemoprotective and therapeutic effects of SFN, alone or in combination with other HDAC inhibitors currently undergoing clinical trials. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|