1. Cytotoxic effects of a doxorubicin-transferrin conjugate in multidrug-resistant KB cells.
- Author
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Fritzer M, Szekeres T, Szüts V, Jarayam HN, and Goldenberg H
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis, Cell Survival drug effects, Clone Cells, DNA, Neoplasm biosynthesis, DNA, Neoplasm drug effects, Doxorubicin analogs & derivatives, Gene Expression, Humans, KB Cells, Kinetics, Receptors, Transferrin metabolism, Thymidine metabolism, Transferrin analogs & derivatives, Tumor Stem Cell Assay, Doxorubicin toxicity, Drug Resistance, Multiple, Transferrin metabolism
- Abstract
Cancer chemotherapy is often limited by the emergence of multidrug-resistant tumor cells. Multidrug resistance (MDR) can be caused by amplification of the MDR genes and overexpression of the P-glycoprotein, which is capable of lowering intracellular drug concentrations. A doxorubicin-transferrin conjugate has been synthesized and exerts its cytotoxic effects through a transmembrane mechanism. We have examined the cytotoxicity of this conjugate and compared it with doxorubicin in sensitive (KB-3-1) and in multidrug-resistant KB cell lines (KB-8-5, KB-C1, and KB-V1). In the clonogenic assay, doxorubicin exhibited IC50 concentrations of 0.03 and 0.12 microM in the sensitive (KB-3-1) and resistant (KB-8-5) cell lines, respectively, whereas, doxorubicin-transferrin conjugate was more effective with IC50 concentrations of 0.006 and 0.028 microM, respectively. In highly multidrug-resistant KB-C1 and KB-V1 cells, doxorubicin up to 1 microM did not cause any cytotoxic effects, while the doxorubicin-transferrin conjugate inhibited colony formation of these cells with IC50 levels of 0.2 and 0.025 microM, respectively. These results demonstrate that doxorubicin-transferrin is effective against multidrug-resistant tumor cells.
- Published
- 1996
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