title: 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.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
authors.forename: Dong-Hun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kwon
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D029662:Betula / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D036381:Diarylheptanoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D004187:Disaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014404:Tubulin / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036381:Diarylheptanoids; D004187:Disaccharides; D056572:Histone Deacetylase Inhibitors; D010936:Plant Extracts; D014404:Tubulin; C000602437:aceroside VIII; D006655:Histone Deacetylases