Inhibition of proliferation and induction of differentiation of human myeloid leukemia cells by novel nucleoside analogs.
Purines such as hypoxanthine and 6-thioguanine have the capacity to induce the differentiation of human myeloid leukemia HL-60 cells in culture. Several nucleoside analogs were synthesized and their effects on cell proliferation and differentiation of HL-60 cells were examined. On incubation with these compounds, proliferation of HL-60 cells was inhibited and the cells were induced to differentiate into morphologically and functionally mature granulocytes. Among the compounds we tested, 2,4-diethyl-7,7,8,8-tetramethyl-cis-2,4-diazabicyclol [4.2.0] octane-3,5-dione was the most effective in inducing differentiation of HL-60 cells. This compound was approximately 100 times more potent on a molar basis than hypoxanthine. The compounds reacted synergistically or additively with a typical antileukemic drug (daunomycin) or another potent differentiation inducer (retinoic acid).
Honma
Y
Y
Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.
Ikuta
T
T
Kasukabe
T
T
Hozumi
M
M
Itoh
T
T
Ogura
H
H
D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D015394:Molecular Structure; D009113:Muramidase / Q000378:metabolism; D009705:Nucleosides / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D009705:Nucleosides; D009113:Muramidase