|
|
 Previous Article | Table of Contents | Next Article 
Comparative cellular pharmacology of daunorubicin and idarubicin in human
multidrug-resistant leukemia cells
E Berman and M McBride
Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY
10021.
We examined the effect of daunorubicin (DNR), the new anthracycline
derivative idarubicin (IDR), and verapamil on two leukemia cell lines that
displayed the multidrug resistant (MDR) phenotype and used laser flow
cytometry to quantitate intracellular anthracycline content. The
vinblastine-resistant human lymphoblastic leukemia cell line CEM-VBL
demonstrated minimal DNR uptake; simultaneous incubation with verapamil and
DNR increased intracellular DNR uptake fourfold. IDR uptake was 10 times
more rapid in these cells and simultaneous incubation with IDR and
verapamil resulted in only a 1.2-fold increase of intracellular IDR.
Similar results were observed in the vincristine-resistant human myeloid
leukemia cell line HL-60/RV+. Intracellular retention of DNR and IDR was
also measured in each cell line. In CEM-BVL cells, 38% of the original DNR
concentration remained after a 2-hour resuspension in fresh medium compared
with 71% of the original IDR concentration. In HL- 60/RV+ cells, 36% of the
DNR concentration remained compared with 51% of the IDR concentration.
After incubation of CEM-VBL and HL-60/RV+ cells with DNR for 1 hour
followed by resuspension in fresh medium plus verapamil, intracellular DNA
retention increased 5- and 5.2-fold, respectively. However, incubation of
these cells for 1 hour with IDR followed by resuspension in fresh medium
plus verapamil resulted in only a 1.6- and 2.4-fold increase in
intracellular IDR retention. Lastly, clonogenic experiments were performed
to correlate intracellular anthracycline content with cytotoxicity. DNR
alone had a minimal effect on the clonogenic growth of CEM-VBL cells,
whereas the combination of DNR plus verapamil resulted in approximately 80%
growth inhibition. However, incubation of these cells with IDR alone
resulted in greater than 95% growth inhibition. These results suggest that
IDR may be more effective than DNR in leukemia cells that display the MDR
phenotype.
Volume 79,
Issue 12,
pp. 3267-3273,
06/15/1992
Copyright © 1992 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. S. Tallman, D. G. Gilliland, and J. M. Rowe
Drug therapy for acute myeloid leukemia
Blood,
August 15, 2005;
106(4):
1154 - 1163.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Solary, B. Drenou, L. Campos, P. de Cremoux, F. Mugneret, P. Moreau, B. Lioure, A. Falkenrodt, B. Witz, M. Bernard, et al.
Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia
Blood,
August 15, 2003;
102(4):
1202 - 1210.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. P. Swift, S. M. Cutts, A. Rephaeli, A. Nudelman, and D. R. Phillips
Activation of Adriamycin by the pH-dependent Formaldehyde-releasing Prodrug Hexamethylenetetramine
Mol. Cancer Ther.,
February 1, 2002;
2(2):
189 - 198.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Toffoli, R. Sorio, P. Aita, D. Crivellari, G. Corona, A. Bearz, I. Robieux, A. M. Colussi, F. Stocco, and M. Boiocchi
Dose-finding and Pharmacologic Study of Chronic Oral Idarubicin Therapy in Metastatic Breast Cancer Patients
Clin. Cancer Res.,
June 1, 2000;
6(6):
2279 - 2287.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. Heilmann, P. Schönfeld, T. Schlüter, R. Bohnensack, and W. Behrens-Baumann
Effect of the cytostatic agent idarubicin on fibroblasts of the human Tenon's capsule compared with mitomycin C
Br. J. Ophthalmol.,
August 1, 1999;
83(8):
961 - 966.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
X. F. Hu, A. Slater, P. Kantharidis, D. Rischin, S. Juneja, R. Rossi, G. Lee, J. D. Parkin, and J. R. Zalcberg
Altered Multidrug Resistance Phenotype Caused by Anthracycline Analogues and Cytosine Arabinoside in Myeloid Leukemia
Blood,
June 15, 1999;
93(12):
4086 - 4095.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-M. Koo, M. Gray-Goodrich, G. Kohlhagen, M. J. McWilliams, M. Jeffers, A. Vaigro-Wolff, W. G. Alvord, A. Monks, K. D. Paull, Y. Pommier, et al.
The ras Oncogene-Mediated Sensitization of Human Cells to Topoisomerase II Inhibitor-Induced Apoptosis
J Natl Cancer Inst,
February 3, 1999;
91(3):
236 - 244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. J. Ketley, P. D. Allen, S. M. Kelsey, and A. C. Newland
Modulation of Idarubicin-Induced Apoptosis in Human Acute Myeloid Leukemia Blasts by All-Trans Retinoic Acid, 1,25(OH)2 Vitamin D3, and Granulocyte-Macrophage Colony-Stimulating Factor
Blood,
December 1, 1997;
90(11):
4578 - 4587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Rowe and M. S. Tallman
Intensifying Induction Therapy in Acute Myeloid Leukemia: Has a New Standard of Care Emerged?
Blood,
September 15, 1997;
90(6):
2121 - 2126.
[Full Text]
[PDF]
|
|
|
|
|
