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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lehnert, M. Articles by Salmon, S. E. Search for Related Content PubMed PubMed Citation Articles by Lehnert, M. Articles by Salmon, S. E. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Synergistic inhibition by verapamil and quinine of P-glycoprotein- mediated multidrug resistance in a human myeloma cell line model M Lehnert, WS Dalton, D Roe, S Emerson and SE Salmon Arizona Cancer Center, University of Arizona College of Medicine, Tucson, AZ 85724. In an effort to develop a clinically useful approach to overcoming P- glycoprotein-mediated multidrug resistance (MDR1), we evaluated combined chemosensitization with verapamil and quinine in a multidrug- resistant (MDR) human myeloma cell line model. In clonogenic assay, verapamil was used at concentrations from 0.1 to 1.0 micrograms/mL, bracketing the plasma levels achieved by oral administration and high- dose intravenous (IV) infusion, respectively. The dose of quinine was held constant at 1.0 micrograms/mL, a plasma concentration readily achieved by oral administration. At each dose level of verapamil tested, the combination with quinine proved more effective than either drug individually in reversing resistance to doxorubicin and vinblastine and synergistic chemosensitizing interaction was observed. Verapamil at 0.1 microgram/mL combined with quinine was capable of restoring sensitivity to doxorubicin fully and reduced resistance to vinblastine as effectively as verapamil alone at 1.0 micrograms/mL. Furthermore, the combination of 1.0 mumol verapamil with 10 mumols quinine increased accumulation and retention of anthracycline in the resistant cells to a greater extent than did either drug individually (P less than .001) and inhibited drug efflux as effectively as verapamil alone at 10 mumols. Our findings suggest that combined chemosensitization with verapamil and quinine may prove useful for overcoming MDR1 in patients with drug-refractory B-cell neoplasms such as multiple myeloma or non-Hodgkin's lymphomas. Volume 77, Issue 2, pp. 348-354, 01/15/1991 Copyright © 1991 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: A. Krishan, K. S. Sridhar, C. Mou, W. D. Stein, E. Lyubimov, Y.-P. Hu, and H. Fernandez Synergistic Effect of Prochlorperazine and Dipyridamole on the Cellular Retention and Cytotoxicity of Doxorubicin Clin. Cancer Res., April 1, 2000; 6(4): 1508 - 1517. [Abstract] [Full Text]

	Copyright © 1991 by American Society of Hematology         Online ISSN: 1528-0020