Chinese Medical Sciences Journal 2002;17(1):27-31

New designed HMBA agents as inducers of erythroleukemia cell differentiation.

Huali WANG 1 ; Shifu ZHANG ; Jianping ZHOU ; Jingbo ZHANG

Affiliations

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Country

China

Language

English

MeSH

Abstract

OBJECTIVESearching for more potent and less toxic HMBA-related agents.

METHODSHuman 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 differentiation of two new designed HMBA derivatives: HMBPA [hexamethylenebi (3-pyridin) amide] and Co-HDTA (ethylenediaminetetra acetic acid cobalt) using cell biology, cytochemical and molecular biology techniques.

RESULTSWe found that the MEL DS19 cells were most sensitive to HMBA (benzidine positive, B+ approximately 76%). Co-HDTA can inhibit the growth of MEL DS19, but induces differentiation just in a small population (B+ 2% approximately 4.5%). Between 0.02 approximately 5 micromol/L, HMBPA induces 3% approximately 8% cells committed to differentiation with little inhibition of cell proliferation. 1 micromol/L HMBPA and 2 mmol/L HMBA together, can obviously increase the percentage of differentiated cell (B+ approximately 72%), inhibit DNA synthesis and accelerate beta-globin transcription.

CONCLUSIONThe new HMBA derivatives may provide potential cancer differentiation inducers.