Induction of differentiation of human myeloid leukemia HL-60 cells by novel pyrimidine nucleoside analogs.

Abstract

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.

• Authors: M Makishima, Y Honma, M Hozumi, K Sampi, M Hattori, I Ishikawa, H Ogura, N Kawahara, T Kanaiwa, K Motoyoshi
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1094 Issue 1 Pg. 1-7 (Aug 13 1991) ISSN: 0006-3002 [Print] Netherlands
• PMID: 1883847 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Pyrimidine Nucleosides
• Ribonucleosides
• TI 79
• Nitroblue Tetrazolium
• Adenosine

Topics

• Adenosine (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cell Differentiation (drug effects)
• Cell Division (drug effects)
• Cell Line
• Granulocytes (drug effects)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, pathology)
• Nitroblue Tetrazolium (chemistry)
• Oxidation-Reduction
• Pyrimidine Nucleosides (chemical synthesis, pharmacology)
• Ribonucleosides (pharmacology)
• Tumor Cells, Cultured