NEW DESIGNED HMBA AGENTS AS INDUCERS OFERYTHROLEUKEMIA CELL DIFFERENTIATION

Searching for more potent and less toxic HMBA related agents. Methods. Human erythroleukemia cell K562, murine erythroleukemia cell (MEL) and its sub line MEL DS19 were used as target cells to select a cell line which is the most sensitive to HMBA, then analyzed the activity of inducing differentiati on of two new designed HMBA derivatives: HMBPA [hexamethylenebi (3 pyridin) ami de] and Co HDTA (ethylenediaminetetra acetic acid cobalt) using cell biology, c ytochemical and molecular biology techniques. Results. We found that the MEL DS19 cells were most sensitive to HMBA (benzidine positive, B+～76%). Co HDTA can inhibit the growth of MEL DS19, but induces differentiation just in a small population (B+ 2%～4.5%). Between 0.02～5μmo l/L, HMBPA induces 3%～8% cells committed to differentiation with little inhib ition of cell proliferation. 1μmol/L HMBPA and 2mmol/L HMBA together, can obvio usly increase the percentage of differentiated cell (B+～ 72%), inhibit DNA sy nthesis and accelerate β globin transcription. Conclusion. The new HMBA derivatives may provide potential cancer differentiatio n inducers.