TY - JOUR
T1 - Isolation and Characterization of an Anthracycline-resistant Human Leukemic Cell Line
AU - Bhalla, Kapil
AU - Hindenburg, Alexander
AU - Taub, Robert N.
AU - Grant, Steven
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1985/8/1
Y1 - 1985/8/1
N2 - An anthracycline-resistant subline of HL-60 promyelocytic leukemia cells (HL-60/AR) has been isolated in vitro by subculturing in progressively higher concentrations of Adriamycin. The resistant cells are capable of sustaining continuous growth in 10-6 M Adriamycin which is more than 50 times the 50% inhibitory dose for the parent line. HL-60/AR expressed variable degrees of cross-resistance to daunorubicin, dihydroxyanthracenedione, vincristine, vinblastine, and actinomycin D, but it remained sensitive to methotrexate and 1-β-D-arabinofuranosylcytosine. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of glycoproteins of HL-60/AR revealed two prominent glycoproteins with molecular weights of 160,000 ± 10,000 and 110,000 ± 10,000 which were not detected in the sensitive cells. Cellular uptake and retention of daunorubicin was studied in the resistant and sensitive cells utilizing digitized video fluorescence microscopy. The sensitive cells accumulated more drug and showed at least 2-fold greater levels of brightness than the resistant cells. Studies of total intracellular accumulation, utilizing 10-6 M [14C]-daunorubicin as a marker, showed a 1-h accumulation of 98 ± 20 pmol/106 cells in HL-60/AR versus 255 ± 25 pmol/106 cells in HL-60. Exposure to nontoxic concentrations of the calcium channel blocker Verapamil (10-5 M) led to enhanced accumulation (175 ± 8 pmol/106 cells) and retention of the drug in HL-60/AR, resulting in increased cytotoxicity in HL-60/AR. These anthracycline-resistant leukemic cells may serve as a valuable experimental model in studying the phenomenon of multiple drug resistance as well as strategies to circumvent it in human myeloid leukemia.
AB - An anthracycline-resistant subline of HL-60 promyelocytic leukemia cells (HL-60/AR) has been isolated in vitro by subculturing in progressively higher concentrations of Adriamycin. The resistant cells are capable of sustaining continuous growth in 10-6 M Adriamycin which is more than 50 times the 50% inhibitory dose for the parent line. HL-60/AR expressed variable degrees of cross-resistance to daunorubicin, dihydroxyanthracenedione, vincristine, vinblastine, and actinomycin D, but it remained sensitive to methotrexate and 1-β-D-arabinofuranosylcytosine. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of glycoproteins of HL-60/AR revealed two prominent glycoproteins with molecular weights of 160,000 ± 10,000 and 110,000 ± 10,000 which were not detected in the sensitive cells. Cellular uptake and retention of daunorubicin was studied in the resistant and sensitive cells utilizing digitized video fluorescence microscopy. The sensitive cells accumulated more drug and showed at least 2-fold greater levels of brightness than the resistant cells. Studies of total intracellular accumulation, utilizing 10-6 M [14C]-daunorubicin as a marker, showed a 1-h accumulation of 98 ± 20 pmol/106 cells in HL-60/AR versus 255 ± 25 pmol/106 cells in HL-60. Exposure to nontoxic concentrations of the calcium channel blocker Verapamil (10-5 M) led to enhanced accumulation (175 ± 8 pmol/106 cells) and retention of the drug in HL-60/AR, resulting in increased cytotoxicity in HL-60/AR. These anthracycline-resistant leukemic cells may serve as a valuable experimental model in studying the phenomenon of multiple drug resistance as well as strategies to circumvent it in human myeloid leukemia.
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M3 - Article
C2 - 3860286
AN - SCOPUS:0021952694
VL - 45
SP - 3657
EP - 3662
JO - Cancer research
JF - Cancer research
SN - 0008-5472
IS - 8
ER -