TY - JOUR
T1 - Cell differentiation effects of 2′-fluoro-1-β-d-arabinofuranosyl pyrimidines in HL-60 cells
AU - Kong, Xiang Bin
AU - Andreeff, Michael
AU - Fanucchi, Michael P.
AU - Fox, Jack J.
AU - Watanabe, Kyoichi A.
AU - Vidal, Pedro
AU - Chou, Ting Chao
N1 - Funding Information:
THE HUMAN promyelocytic leukemic cell line, HL-60 \[1, 2\], can be induced to differentiate into functional monocytes, granulocytes and macrophages by a number of agents. These agents include dimethyl sulfoxide (DMSO) \[3, 4\], hexamethylene bisacetamide (HMBA), 12-O-tetradecanoyl-phorbol-13-acetate (TPA) \[5,6\], * This work was supported by National Cancer Institute Grants CA18856, CA27569, CA41305 and the Elsa U. Pardee Foundation.
PY - 1987
Y1 - 1987
N2 - 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.
AB - 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.
KW - Cell differentiation
KW - HL-60
KW - pyrimidine analogs
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U2 - 10.1016/0145-2126(87)90123-8
DO - 10.1016/0145-2126(87)90123-8
M3 - Article
C2 - 3480397
AN - SCOPUS:0023584394
SN - 0145-2126
VL - 11
SP - 1031
EP - 1039
JO - Leukemia Research
JF - Leukemia Research
IS - 11
ER -