Apicidin, a histone deacetylase inhibitor, induces differentiation of HL-60 cells.
The fungal metabolite apicidin (cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecanoyl)) inhibited the growth of HL-60 cells in a concentration-dependent manner (100-1000 nM). At higher concentrations (>300 nM), cell death was induced. At 100 nM, it induced hyperacetylation of histone H4 time-dependently, while trichostatin A induced transient hyperacetylation. Apicidin (10-100 nM) increased the cells having nitroblue tetrazolium-reducing activity and expressing CD11b but not CD14 and CD15. The expression of CD11b by apicidin was long lasting, while that by trichostatin A was transient. In K562 cells, apicidin at 10-100 nM did not inhibit cell growth nor express CD11b, CD14 and CD15. Our findings indicate that apicidin inhibits proliferation and induces the early stage of differentiation of HL-60 cells.
Hong
JangJa
J
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Ishihara
Kenji
K
Yamaki
Kouya
K
Hiraizumi
Kenji
K
Ohno
Tadao
T
Ahn
Jong Woong
JW
Zee
OkPyo
O
Ohuchi
Kazuo
K
D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D039481:CD11b Antigen / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D016256:Lewis X Antigen / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects
D039481:CD11b Antigen; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D016256:Lewis X Antigen; D018950:Lipopolysaccharide Receptors; D009363:Neoplasm Proteins; D010456:Peptides, Cyclic; C102351:apicidin