Relationship of multidrug resistance to rhodamine-123 selectivity between carcinoma and normal epithelial cells: taxol and vinblastine modulate drug efflux.
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) all of 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.
Brouty-Boyé
D
D
Department of Cell Biology and Anatomy, University of Miami, School of Medicine, Fl 33101, USA.
Kolonias
D
D
Wu
C J
CJ
Savaraj
N
N
Lampidis
T J
TJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D001483:Base Sequence; D001940:Breast; D001943:Breast Neoplasms; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D018432:Drug Resistance, Multiple / Q000235:genetics; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism* / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D012235:Rhodamines; D020112:Rhodamine 123; D014747:Vinblastine; D017239:Paclitaxel