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STUDY ON TWO NOVEL VITAMIN D3 ANALOGUES WITHPOTENT EFFECTS ON THE GROWTH ANDDIFFERENTIATION OF LEUKEMIA CELLS

Cheng Tao ; Song Liangnian;Li Chuansheng ;el al(Changhai Hospijal , Second Militaty Medical University ,Shanghai , 200433)  
n order to find out new more potent differentiationinducers, We tested the effects of two novel vitamin D3analogues-EB1089 and MC903, and compared themwith 1 , 25-dihydroxyvrtamin D3 ( 1 , 25 (OH )_2D_3 ) , on thegrowth and differentiation of two human leukemic celllines (HL-60 and HIMeg-1 ). Colony formation testshowed that EB1089, MC903 and 1 , 25 (OH)_2D_3 couldinhibit the clonal growth markedly with ED50 doses of 9× 10 ̄(-9)mol/L, 10 × 10  ̄(-9)mol/L , 70×10 ̄(-9)mol/L. for HL-60 cells and with that of 7 × 10 ̄(-11)mol/L, 45 × 10  ̄(-11)mol/L, 1000 × 10  ̄(-11) mol/L, for HIMeg-1 cells, respec-tively. Meanwhile, the leukemic cells could be inducedinto rnore mature cells in Monotoid lineage, which wereconfirnied hy morphology examination . nitro letrozoliumblue reduction test and differentiation antigens assay.The cell cycle analysis measured hy flow cytometry alsoshowed the decrease of S phase cells in company with in-crease of G0 /G1 phase cells. Dot blot analysis showedlow levels of C-myc mRNA after the treatment of the drugs on HIMeg-1 cells. It was concluded that EB1089was much more potent than 25 (OH)_2D_2. and MC903 wascomparable to it on the growth and differentiation of theleukemic cells. In contrast. these two novel cornooundsappeared to be markedly less toxic than 1 , 25 (OH)_2D_3 inthe tnduction of hypercalcemia. So , both of EB1089 andMC903, especially the former, might hold promise asnew therapeutic agents in the treatment of leukemia andOther cancers.
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