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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brouty-Boyé, D. Articles by Lampidis, T. J. Search for Related Content PubMed PubMed Citation Articles by Brouty-Boyé, D. Articles by Lampidis, T. J.

Relationship of Multidrug Resistance to Rhodamine-123 Selectivity between Carcinoma and Normal Epithelial Cells: Taxol and Vinblastine Modulate Drug Efflux¹

Department of Cell Biology and Anatomy, University of Miami, School of Medicine, and Sylvester Comprehensive Cancer Center [D. B-B., D. K., T. J. L.] and V.A. Hospital [C. J. W., N. S.], Miami, Florida 33101

Preferential retention and cytotoxicity of Rhodamine-123 (Rho-123) was originally reported in a number of carcinoma cell types isolated from a variety of tissues as compared to normal epithelial cells from a limited number of other tissues. In the present study, we have examined Rho-123 selectivity in normal and tumor cell lines isolated from the same tissue source, i.e., human breast. We found that: (a) in matched pairs of normal and carcinoma breast cells, Rho-123 displays no preferential retention in either cell type; (b) there is no preferential toxicity in carcinoma as compared to normal breast cells; in fact, one of the carcinoma cell lines (MDA-MB231) shows moderate resistance to this dye; (c) allof the human breast cell lines do not express P-glycoprotein-mediated multidrug resistance; (d) the normal monkey kidney epithelial cell line CV-1, which was originally used as a model to demonstrate the relative resistance of normal epithelial cells to this drug, is found to express high levels of the mdr-1 gene, is resistant to other multidrug-resistant drugs (taxol and vinblastine), and its resistance to Rho-123 as well as decreased Rho-123 retention can be reversed by verapamil; and (e) taxol and vinblastine are found to block increased Rho-123 efflux in CV-1 cells. Thus, overall the data suggest that preferential retention and cytotoxicity of Rho-123 in carcinoma versus normal epithelial cells is related to the differential expression of the mdr-1 gene.

¹ Supported in part by USPHS NIH Grant CA 37109 and a national V.A. grant.

² Visiting scientist on leave from the Institut de la Santé et de la Recherche Médicale, Paris, France.

³ To whom requests for reprints should be addressed, at Department of Cell Biology and Anatomy, University of Miami, School of Medicine (R-124), P.O. Box 016960, Miami, FL 33101.

Received 1/11/95. Accepted 3/ 3/95.

This article has been cited by other articles:

				K. Miller, M. Wang, J. Gralow, M. Dickler, M. Cobleigh, E. A. Perez, T. Shenkier, D. Cella, and N. E. Davidson Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast Cancer N. Engl. J. Med., December 27, 2007; 357(26): 2666 - 2676. [Abstract] [Full Text] [PDF]

				J. G. Sarver, W. A. Klis, J. P. Byers, and P. W. Erhardt Microplate Screening of the Differential Effects of Test Agents on Hoechst 33342, Rhodamine 123, and Rhodamine 6G Accumulation in Breast Cancer Cells that Overexpress P-Glycoprotein J Biomol Screen, February 1, 2002; 7(1): 29 - 34. [Abstract] [PDF]

				Y.-Y. LIU, T.-Y. HAN, A. E. GIULIANO, and M. C. CABOT Ceramide glycosylation potentiates cellular multidrug resistance FASEB J, March 1, 2001; 15(3): 719 - 730. [Abstract] [Full Text] [PDF]