Abstract
Drug resistance is one of the most important problems of cancer chemotherapy. Chemoresistance may appear at initial presentation or at the time of relapse. Several mechanisms of drug resistance have been identified by in vitro studies, using highly resistant cell lines. Several genes could be characterized capable of conferring resistance to chemotherapeutic agents. Among these genes the multidrug resistance gene (MDR-1) has been extensively studied because its overexpression can lead to resistance to anthracyclines, vinca alkaloids and probably podophyllotoxins. MDR-1 gene, mapping to chromosome 7 (q 21–31), encodes a membrane glycoprotein of 170 kDa, P 170, which acts as an ATP-dependent drug efflux pump, transporting many organic, widely unrelated compounds leading to low intracellular drug concentrations (Dano, Danks, Glisson, Thiebaut, Ling, Gros, Endicott, Roninson).
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Dano K (1972) Cross resistance between vinca alkaloids and anthracyclines in Ehrlich ascites tumor in vivo. Cancer Chemother. Rep 56: 701
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
Glisson B, Gupta R, Hoedges P et al. (1986) Cross resistance to intercalating agents in an epidephyllotoxin resistant chinese hamster ovary cell line: evidence for an common intracellular target. Cancer Res 46: 1939
Thiebaut F, Tsuruo T, Hamada H, Gottesman, MM, Pastan I, Willingham MC (1987) Cellular localization of the multidrug resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 84: 7735
Ling V, Kartner N, Sudo T, Siminowitch L, Riordan JR (1983) Multi drug resistance phenotype in Chinese hamster ovary cells. Cancer Treat Rep 67: 869
Gros P, Croop J, Houseman D (1986) Mammalian multi drug resistance gene: Complete CDNA sequence indicates stron homology to bacterial transport proteins cell 47: 371
Endicott JA., Ling V (1989) The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem 58: 137
Roninson IB, Chin JE, Choi K, Gros P, Houseman D, Fojo A, Shen D, Gottesman MM, Pastan I (1986) Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci USA 83: 4538
Marie JP, Zittoun R, Sikie BI (1991) Multidrug resistance (mdrl) gene expression in adult leukemias: Correlations with treatment outcome and in vitro drug sensitivity. Blood 78: 586
Campos L, Guyotat D, Archimbaud E, CalmardOriol P, Tsuruo T, Troncy J, Treille D, Fiere D (1992) Clinical significance of multidrug resistance P-glycoprotein (P-170) expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood 79: 473
Tsuruo T (1983) Reversal of acquired resistance to vinca alkaloids and anthracycline antibiotics. Cancer Treat Rep 67: 889
Ozolz R, Cunnion RE, Klecker RW jr, Hamilton TC, Ostchega Y, Parillo JE, Young RC (1987) Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients. J Clin Oncol 5: 641
Rogan AM, Hamilton TC, Young RC, Klecher RW jr, Ozolz RF (1984) Reversal of adriamycin resistance by verapamil in human ovarian cancer. Science 224: 994
Dalton WS, Grogan TM, Meltzer PS, Scheper RJ, Durie BGM, Taylor CW, Miller TP, Salmon SE (1989) Drug-resistance in multiple myeloma and non-Hodgin’s lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. J Clin Oncol 7: 415
Häußermann K, Benz B, Gekeler V, Schumacher K, Eichelbaum M (1990) Effects of verapamil emantioners and major metabolites on the cytotoxicity of vincristine and daunomycin in human lymphoma cell lines. Eur J Pharmacol 40: 53
Schumacher K, Ladda E, Bühl K, Weimer A, Eser C, Hamprecht K, Traugott U, Roller E, Schalk KP and Eichelbaum M (1991) R-verapamil, a modulator of mutli drug resistance: Phase I clinical trial J Cancer Res Clin Oncol 117 (Suppl.) 113
Haber DA (1992) Multidrug resistance (MDR1) in leukemia: Is it time to test? Blood 79: 295
Gross AS, Heuer B, and Eichelbaum M (1988) Stereoselective proteinbinding of verapamil enantiomers. Biochem Pharmacol 37;4623
Pennock GD, Dalton WS, Roeske WR, Appleton CP, Mosley K, Plezia P, Miller TP, Salmon SE (1991) Systemic toxic effects associated with high-dose verapamil infusion and chemotherapy administration. J Natl Cancer Inst 83: 105
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Schumacher, K. et al. (1994). Reversal of Multidrug Resistance by R-Verapamil. In: Büchner, T., Hiddemann, W., Wörmann, B., Schellong, G., Ritter, J. (eds) Acute Leukemias IV. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 36. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78350-0_42
Download citation
DOI: https://doi.org/10.1007/978-3-642-78350-0_42
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-78352-4
Online ISBN: 978-3-642-78350-0
eBook Packages: Springer Book Archive