Induction of differentiation of human myeloid leukemia HL-60 cells by novel pyrimidine nucleoside analogs.
New pyrimidine nucleoside analogs (18 compounds) were synthesized and their growth-inhibiting and differentiation-inducing activities on human myeloid leukemia HL-60 cells were examined. Some of the analogs were found to induce nitroblue tetrazolium (NBT) reducing activity in the HL-60 cells. The inducing activities of these compounds were compared at their concentrations for 50% inhibition of cell growth. TI-79 (3-benzyl-5-methyl-3-(beta-D-ribofuranosyl)pyrido[2,3-d]pyrimidine- 2,4(1H,3H)-dione) was a very effective inducer of NBT-reduction and of differentiation of the cells into mature granulocytes. The induction of NBT-reducing activity by TI-79 was inhibited by high concentrations of the natural nucleoside, adenosine. Other differentiation inducers, such as retinoic acid, 1 alpha,25-dihydroxyvitamin D-3 and staurosporin markedly enhanced the induction of differentiation of HL-60 cells by TI-79. Nucleoside analogs such as TI-79 should be useful for differentiation therapy of some types of myelogenous leukemia.
Makishima
M
M
Saitama Cancer Center, Japan.
Honma
Y
Y
Hozumi
M
M
Sampi
K
K
Hattori
M
M
Ishikawa
I
I
Ogura
H
H
Kawahara
N
N
Kanaiwa
T
T
Motoyoshi
K
K
D000241:Adenosine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D009580:Nitroblue Tetrazolium / Q000737:chemistry; D010084:Oxidation-Reduction; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D012263:Ribonucleosides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011741:Pyrimidine Nucleosides; D012263:Ribonucleosides; C070713:TI 79; D009580:Nitroblue Tetrazolium; D000241:Adenosine