Effects of rare earth compounds on growth and apoptosis of leukemic cell lines

Summary

To explore a new agent for inhibiting leukemic cells, we investigated the effects of rare earth compounds (lanthanum chloride and cerium chloride) on the growth and apoptosis of HL-60 and NB4 cells. The growth of HL-60 and NB4 cells was tested by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) colorimetric assay. The apoptosis was measured by light microscopy, flow cytometry, and terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) method. The effect of LaCl₃ on normal bone marrow hematopoietic progenitor cells was evaluated by colony-forming unit-granulocyte-macrophage (CFU-GM) assay. Under our experimental conditions, MTT assay showed that 48-h treatment with 1, 2, and 3 mM LaCl₃ or 48- and 72-h treatments with 1 mM LaCl₃ could significantly inhibit the growth of HL-60 cells. Treatment with 2 and 4 mM CeCl₃ for 72 h could significantly inhibit the growth of NB4 cells. Apoptosis could be detected on treatment with 2 mM LaCl₃ for 24 h in HL-60 cells by light microscopic morphology examination, flow cytometric analysis, and TUNEL method. Apoptosis could be also detected on treatment with 2 mM CeCl₃ for 72 h in NB4 cells. Treatment with 1 mM LaCl₃ could arrest the transitions from GO/G1 to S phase. The granulocyte-macrophage colony formation of normal bone marrow cells was not significantly inhibited at lower concentrations of LaCl₃ (0.5 to 2 mM). Our results indicate that at certain concentrations, the rare earth compounds may inhibit the growth of leukemic cells, induce them to apoptosis, and have no significant inhibitory effects on normal bone marrow hematopoietic progenitor cells (CFU-GM). The mechanism needs to be further investigated.