New designed HMBA agents as inducers of erythroleukemia cell differentiation.
OBJECTIVE
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 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.


RESULTS
We 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.


CONCLUSIONS
The new HMBA derivatives may provide potential cancer differentiation inducers.
Wang
Huali
H
Department of Cell Biology, Institute of Basic Medical Sciences, CAMS & PUMC, Beijing 100005.
Zhang
Shifu
S
Zhou
Jianping
J
Zhang
Jingbo
J
D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D000081:Acetamides; D000970:Antineoplastic Agents; D011725:Pyridines; D012333:RNA, Messenger; C481722:hexamethylenebi (3-pyridin) amide; D005914:Globins; C014026:hexamethylene bisacetamide