TY - JOUR
T1 - Induction of morphological and functional differentiation of human myeloid leukemia cells (HL-60 and LK) by a benzoic acid derivative of retinoic acid
AU - Fabian, Ina
AU - Shvartzmayer, Sara
AU - Fibach, Eitan
PY - 1987
Y1 - 1987
N2 - In previous studies we have shown that the synthetic retinoid (E)-4[2-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl-1-propenylbenzoic acid (TTNPB) stimulates the growth of myeloid progenitors from normal and myelodysplastic patients. In the present study we compared TTNPB with 13-cis-retinoic acid (RA) in its potential to inhibit cell growth and to induce morphological differentiation and functional activity in two cell lines established in vitro from either acute promyelocytic (HL-60) or acute myelomonocytic (LK) patients. Both agents, 10-6 M, were found to effectively inhibit cell growth and cause a significant decrease in number of immature granulocytes in both cell lines. However, while in HL-60 cells this decrease was associated with a concomitant increase in fully mature granulocytes (neutrophil-like cells) the maturation of LK cells was blocked at the metamyelocyte stage. Study of the functional activity of the induced cells revealed that the rate of superoxide (O2-) production, as assayed by superoxide dismutase-inhibitable ferricytochrome c reduction, was faster in RA treated HL-60 cells than in TTNPB treated cells (0.41 vs 0.25 nmol. O2-/106 cells/60 min). Superoxide production by LK cells treated by either TTNPB or RA was negligible. The percentage of O2--producing cells was determined cytochemically by their ability to reduce the dye nitroblue tetrazolium (NBT). The results showed that production of O2- by LK cells exposed to TTNPB or RA was negligible by this method as well. A higher percentage of HL-60 cells reduced NBT following incubation with RA than with TTNPB (93 ± 4% vs 26 ± 2%), but neither of the two retinoids affected the ability of LK cells to reduce NBT. TTNPB thus proved less effective than RA in inducing morphological and functional differentiation in HL-60 cells, whereas in LK cells both agents inhibited cell growth but induced only partial cell differentiation.
AB - In previous studies we have shown that the synthetic retinoid (E)-4[2-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl-1-propenylbenzoic acid (TTNPB) stimulates the growth of myeloid progenitors from normal and myelodysplastic patients. In the present study we compared TTNPB with 13-cis-retinoic acid (RA) in its potential to inhibit cell growth and to induce morphological differentiation and functional activity in two cell lines established in vitro from either acute promyelocytic (HL-60) or acute myelomonocytic (LK) patients. Both agents, 10-6 M, were found to effectively inhibit cell growth and cause a significant decrease in number of immature granulocytes in both cell lines. However, while in HL-60 cells this decrease was associated with a concomitant increase in fully mature granulocytes (neutrophil-like cells) the maturation of LK cells was blocked at the metamyelocyte stage. Study of the functional activity of the induced cells revealed that the rate of superoxide (O2-) production, as assayed by superoxide dismutase-inhibitable ferricytochrome c reduction, was faster in RA treated HL-60 cells than in TTNPB treated cells (0.41 vs 0.25 nmol. O2-/106 cells/60 min). Superoxide production by LK cells treated by either TTNPB or RA was negligible. The percentage of O2--producing cells was determined cytochemically by their ability to reduce the dye nitroblue tetrazolium (NBT). The results showed that production of O2- by LK cells exposed to TTNPB or RA was negligible by this method as well. A higher percentage of HL-60 cells reduced NBT following incubation with RA than with TTNPB (93 ± 4% vs 26 ± 2%), but neither of the two retinoids affected the ability of LK cells to reduce NBT. TTNPB thus proved less effective than RA in inducing morphological and functional differentiation in HL-60 cells, whereas in LK cells both agents inhibited cell growth but induced only partial cell differentiation.
KW - Differentiation
KW - leukemia cells
UR - http://www.scopus.com/inward/record.url?scp=0023074610&partnerID=8YFLogxK
U2 - 10.1016/0145-2126(87)90130-5
DO - 10.1016/0145-2126(87)90130-5
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AN - SCOPUS:0023074610
SN - 0145-2126
VL - 11
SP - 863
EP - 868
JO - Leukemia Research
JF - Leukemia Research
IS - 10
ER -
