Abstract
Resistance to chemotherapy continues to be a major impediment and intellectual challenge to the cure of neoplastic diseases, and leukemias are no exception. Resistance of tumor cells to multiple “natural product” anticancer drugs, known as multidrug resistance (MDR), is now a well-documented phenomenon, and some excellent reviews have recently summarized its pharmacology and cell and molecular biology [1–5]. It is now clear that several types of natural product MDR exist experimentally: one is associated with P-glycoprotein (Pgp) over-expression (Pgp-MDR) [1–5], another with alterations in DNA topoisomerase II (at-MDR) (reviewed in [6]), and a third with features similar to Pgp-MDR but without Pgp overexpression [7, 8]. Although PgpMDR appears to have clinical correlates, we do not yet know about the clinical relevance of other forms of MDR. In this chapter, we focus on at-MDR.
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References
Beck WT (1987) The cell biology of multiple drug resistance. Biochem Pharmacol 36: 2879–2887
Moscow JA, Cowan KH (1988) Multidrug resistance. JNCI 80: 14–20
Endicott JA, Ling V (1989) The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem 58: 137–171
Van der Bliek AM, Borst P (1989) Multidrug resistance. Adv Cancer Res 52: 165–203
Roninson IB (1991) Molecular and cellular biology of multidrug resistance in tumor cells. Plenum, New York
Beck WT, Danks MK (1991) Multidrug resistance associated with alterations in topoisomerase II. In: Potmesil M, Kohn K (eds) DNA topoisomerases in cancer. Oxford University Press, New York pp. 260–275
Hindenburg AA, Gervasoni JE Jr, Krishna S, Stewart VJ, Rosado M, Lutzky J, Bhalla K, Baker MA, Taub RN (1989) Intracellular distribution and pharmacokinetics of daunorubicin in anthracycline-sensitive and -resistant HL-60 cells. Cancer Res 49: 4607–4614
McGrath T, Center MS (1988) Mechanisms of multidrug resistance in HL60 cells: evidence that a surface membrane protein distinct from P-glycoprotein contributes to reduced cellular accumulation of drug. Cancer Res 48: 3959–3963
Beck WT (1990) Mechanisms of multidrug resistance in human tumor cells. The roles of P-glycoprotein, DNA topoisomerase II, and other factors. Cancer Treat Rev 17 (Suppl A): 11–20
Danks MK, Yalowich JC, Beck WT (1987) Atypical multiple drug resistance in a human leukemic cell line selected for resistance to teniposide (VM-26). Cancer Res 47: 1297–1301
Beck WT, Cirtain MC, Danks MK, Felsted RL, Safa AR, Wolverton JS, Suttle DP, Trent JM (1987) Pharmacological, molecular, and cytogenetic analysis of “atypical” multidrugresistant human leukemia cells. Cancer Res 47: 5455–5460
Wolverton JS, Danks MK, Schmidt CA, Beck WT (1989) Genetic characterization of the multidrug-resistant phenotype of VM26-resistant human leukemic cells. Cancer Res 49: 2422–2426
Danks MK, Schmidt CA, Suttle DP, Beck WT (1988) Altered catalytic activity of and DNA cleavage by DNA topoisomerase II from human leukemic cells selected for resistance to VM-26. Biochemistry 27: 8861–8869
Deffie AM, Batra JK, Goldenberg GJ (1989) Direct correlation between DNA topoisomerase II activity and cytotoxicity in adriamycin-sensitive and resistant P388 leukemia cell lines. Cancer Res 49: 58–62
Matsuo K, Kohno K,Takano H, Sato S, Kiue A, Kuwano M (1990) Reduction of drug accumulation and DNA topoisomerase II activity in acquired teniposide-resistant human cancer KB cell lines. Cancer Res 50: 5819–5824
Danks MK, Schmidt CA, Deneka DA, Beck WT (1989) Increased ATP requirement for activity of and complex formation by DNA topoisomerase II from human leukemic CCRF-CEM cells selected for resistance to teniposide. Cancer Commun 1: 101–109
Fernandes DJ, Smith-Nanni C, Paff MT, Neff T-A (1988) Effects of antileukemia agents on nuclear matrix-bound DNA replication in CCRF-CEM leukemia cells. Cancer Res 48: 1850–1855
Fernandes DJ, Danks MK, Beck WT (1990) Decreased nuclear matrix DNA topoisomerase Il in human leukemia cells resistant to VM-26 and m-AMSA. Biochemistry 29: 4235–4241
Bugg BY, Danks MK, Beck WT Suttle DP (1991) Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide. Proc Natl Acad Sci USA 88: 7654–7658
Goldstein LJ, Galski H, Fojo A, Willingham M, Lai SL. Gazdar A, Pirker R, Green A, Crist W, Brodeur GM, Lieker M, Crossman J, Gottesman MM, Pastan I (1989) Expression of a multidrug resistance gene in human cancers. JNCI 81: 116–124
Trask DK, DiDonato JA, Muller MT (1984) Rapid detection and isolation of covalent DNA/protein complexes: application to topoisomerase I and II. EMBO J 3: 671–676
Zwelling LA, Hinds M, Chan D, Mayes J, Sie KL, Parker E, Silberman L, Radcliffe A, Beran M, Blick M (1989) Characterization of an amsacrine-resistant line of human leukemia cells. J Biol Chem 264: 16411–16420
Qian X-d, Beck WT (1990) Binding of an optically pure photoaffinity analogue of verapamil, LU-49888, to P-glycoprotein from multidrug resistant human leukemic cell lines. Cancer Res 50: 1132–1137
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© 1992 Springer-Verlag Berlin Heidelberg
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Beck, W.T., Funabiki, T., Danks, M.K. (1992). The Role of DNA Topoisomerase II in Multidrug Resistance in Human Leukemia. In: Hiddemann, W., Büchner, T., Wörmann, B., Plunkett, W., Keating, M., Andreeff, M. (eds) Acute Leukemias. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 34. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76591-9_2
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DOI: https://doi.org/10.1007/978-3-642-76591-9_2
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