Aceroside VIII is a new natural selective HDAC6 inhibitor that synergistically enhances the anticancer activity of HDAC inhibitor in HT29 cells.

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.

• 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)
• 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

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)