Cell differentiation effects of 2′-fluoro-1-β-D-arabinofuranosyl pyrimidines in HL-60 cells Journal Article
| Authors: | Kong, X. B.; Andreeff, M.; Fanucchi, M. P.; Fox, J. J.; Watanabe, K. A.; Vidal, P.; Chou, T. C. |
| Article Title: | Cell differentiation effects of 2′-fluoro-1-β-D-arabinofuranosyl pyrimidines in HL-60 cells |
| Abstract: | A group of 2′-fluoro and 5-substituted arabinosyl pyrimidines and a group of base-substituted pseudoisocytidine analogs were evaluated for their capacity to induce differentiation in the human promyelocytic leukemia cell line, HL-60. These compounds were compared to 1-β-d-arabinofuranosylcytosine (Ara-C) by monitoring: (1) inhibition of cell growth; (2) morphological maturation; (3) nitroblue tetrazolium (NBT) reduction; (4) expression of a myeloid differentiation antigen, Mol; and (5) inhibition of colony formation. Exposure of logarithmically growing cells for 5 days to Ara-C, 2′-fluoro-Ara-C (FAC), 2′-fluoro-5-methyl-Ara-C (FMAC) and 2′-fluoro-5-ethyl-Ara-C (FEAC) resulted in cell growth inhibition at ED50 concentrations of 0.007, 0.11, 1.7 and 18 μM, and at cytostatic concentrations of 0.1, 0.5, 5.0 and 50 μM, respectively. These compounds induced granulocytic and monocytic maturation, reduction of NBT, increased expression of Mol antigen and a decrease or loss of both cell proliferation and colony formation in semisolid medium. There were few, if any, cell differentiation effects for the uracil nucleosides and pseudoisonucleosides tested. We found that Ara-C was the most cytotoxic of the compounds, and that when comparing absolute numbers of differentiated cells, i.e. percent of positive cells multiplied by the number of viable cells, FAC, FMAC and FEAC were superior to Ara-C in inducing differentiation of HL-60 cells. © 1987. |
| Keywords: | clinical article; human cell; comparative study; cytarabine; cell division; cell differentiation; tumor cells, cultured; pyrimidines; kinetics; leukemia, myeloid; promyelocytic leukemia; clone cells; antigens, differentiation; arabinonucleosides; hl-60; human; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; nitroblue tetrazolium; pyrimidine analogs |
| Journal Title: | Leukemia Research |
| Volume: | 11 |
| Issue: | 11 |
| ISSN: | 0145-2126 |
| Publisher: | Elsevier Ltd |
| Date Published: | 1987-01-01 |
| Start Page: | 1031 |
| End Page: | 1039 |
| Language: | English |
| DOI: | 10.1016/0145-2126(87)90123-8 |
| PUBMED: | 3480397 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 February 2021 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work