Anti-parasitic activity of depudecin on Neospora caninum via the inhibition of histone deacetylase.
Neospora caninum is an apicomplexan parasite associated with abortion in cattle worldwide. Apicidin, histone deacetylase (HDAC) inhibitor, has shown a broad spectrum of anti-protozoal activity against apicomplexan parasites. Cultured vero cells infected with N. caninum tachyzoites were treated with 0.5 microg/ml of depudecin, another known natural product isolated from Altermaria brassiciicola with anti-histone deacetylase activity, to examine the efficacy of depudecin against intracellular multiplication of N. caninum tachyzoite, using 15 ng/ml of apicidin as the control. Depudecin significantly inhibited the intracellular multiplication of N. caninum at a level similar to that of apicidin without exerting any cytotoxicity on the host vero cells. Acid/urea/Triton gel electrophoresis analysis show anti-parasitic activity of depudecin appears to be due to the inhibition of protozoal histone deacetylase, which induces hyperacetylation of histones in N. caninum.
Kwon
Ho Jeong
HJ
Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, South Korea.
Kim
Jae-Hoon
JH
Kim
Minjung
M
Lee
Jung-Keun
JK
Hwang
Woo-Suk
WS
Kim
Dae-Yong
DY
D000466:Alkadienes / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology* / Q000633:toxicity; D005233:Fatty Alcohols / Q000494:pharmacology* / Q000633:toxicity; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D018688:Neospora / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014709:Vero Cells
D000466:Alkadienes; D000981:Antiprotozoal Agents; D004852:Epoxy Compounds; D005233:Fatty Alcohols; D056572:Histone Deacetylase Inhibitors; D006657:Histones; C072251:depudecin; D006655:Histone Deacetylases