Abstract |
The identification of new isoform-specific histone deacetylase inhibitors is important for revealing the biological functions of individual histone deacetylase and for determining their potential use as therapeutic agents. Among the 11 zinc-dependent histone deacetylases that have been identified in humans, histone deacetylase 6 is a structurally and functionally unique enzyme. Here, we tested the inhibitory activity of diarylheptanoids isolated from Betula platyphylla against histone deacetylase 6. Aceroside VIII selectively inhibited histone deacetylase 6 catalytic activity and the combined treatment of aceroside VIII or (-)- centrolobol with A452, another selective histone deacetylase 6 inhibitor, led to a synergistic increase in levels of acetylated α- tubulin. Aceroside VIII, paltyphyllone, and (-)- centrolobol synergistically enhanced the induction of apoptosis and growth inhibition by A452. Consistent with these results, A452 in combination with aceroside VIII, paltyphyllone, or (-)- centrolobol was more potent than either drug alone for the induction of apoptosis. Together, these findings indicate that aceroside VIII is a specific histone deacetylase 6 inhibitor and points to a mechanism by which natural histone deacetylase 6-selective inhibitors may enhance the efficacy of other histone deacetylase 6 inhibitors in colon cancer cells.
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Authors | Hyun-Wook Ryu, Dong-Hun Lee, Dong-Hee Shin, Seung Hyun Kim, So Hee Kwon |
Journal | Planta medica
(Planta Med)
Vol. 81
Issue 3
Pg. 222-7
(Feb 2015)
ISSN: 1439-0221 [Electronic] Germany |
PMID | 25590368
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Georg Thieme Verlag KG Stuttgart · New York. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Diarylheptanoids
- Disaccharides
- Histone Deacetylase Inhibitors
- Plant Extracts
- Tubulin
- aceroside VIII
- Histone Deacetylases
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Topics |
- Acetylation
- Adenocarcinoma
(drug therapy, metabolism)
- Antineoplastic Agents, Phytogenic
(isolation & purification, pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Betula
(chemistry)
- Colonic Neoplasms
(drug therapy, metabolism)
- Diarylheptanoids
(chemistry, isolation & purification, pharmacology, therapeutic use)
- Disaccharides
(chemistry, isolation & purification, pharmacology, therapeutic use)
- HT29 Cells
- Histone Deacetylase Inhibitors
(isolation & purification, pharmacology, therapeutic use)
- Histone Deacetylases
(metabolism)
- Humans
- Phytotherapy
- Plant Extracts
(chemistry, pharmacology, therapeutic use)
- Tubulin
(metabolism)
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