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.