Effect of Homoharringtonine on Proliferation and Differentiation

Homoharringtonine (HHT) is a cephalotaxine ester derived from an evergreen tree of southern China. We studied the effect of HHT on the clonal proliferation and differentiation of human leukemic cells from cell lines and patients. Dose-response studies found that HHT inhibited colony formation of myeloid cell lines (50% inhibitory dose range, 7 to 12 nu/ml), lymphocytic cell lines (50% inhibitory dose range, 4 to 7 ng/ ml), and fresh leukemic cells (50% inhibitory dose range, 2 to 25 ng/ml). Pulse-exposure studies showed that colony formation of HL-60 cells was inhibited 50% by HHT (10 to 20 ng/ml) at 45 h and completely inhibited at 72 h. Radioactive precursor studies using III 60 cells showed that HHT predominantly inhibited protein synthesis as compared with RNA and DNA synthesis. Taking advantage of this, we have found that the combination of HHT with l-/3-i>arabinofuranosylcytosine (inhibitor of DNA synthesis) was synergistic in the inhibition of HL-60 clonal growth. HHT (2 to 20 ng/ml) also was found to induce up to 28% of HL-60 cells to differentiate toward macrophage-like cells.