Aceroside VIII is a new natural selective hdac6 inhibitor that synergistically enhances the anticancer activity of HDAC inhibitor in HT29 cells

Hyun Wook Ryu, Dong Hun Lee, Dong Hee Shin, Seung Hyun Kim, So Hee Kwon

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)222-227
Number of pages6
JournalPlanta Medica
Volume81
Issue number3
DOIs
Publication statusPublished - 2015 Feb

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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