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Lacidipine and josamycin: two new multidrug resistance modulators
L Crosta1, V Candiloro, M Meli
1Istituto di Farmacologia, Università di Palermo, Italy.
Anticancer Research
|November 1, 1994
Summary
This study explores reversing multidrug resistance (MDR) in cancer cells using daunomycin with lacidipine or josamycin. These agents effectively reversed MDR without increasing daunomycin accumulation, suggesting novel therapeutic strategies.
Area of Science:
- Pharmacology
- Cancer Biology
- Drug Resistance
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy, limiting the efficacy of cytotoxic drugs.
- Murine erythroleukemia cell lines provide a model for studying MDR mechanisms and evaluating reversal agents.
Purpose of the Study:
- To evaluate the efficacy of lacidipine (LCD) and josamycin (JSM) in reversing daunomycin (DNM) resistance in a murine erythroleukemia cell line.
- To compare the MDR reversal activity of LCD and JSM with established agents like verapamil (VRP) and erythromycin (ERY).
- To investigate the effect of these modulators on DNM accumulation in resistant cells.
Main Methods:
- Treatment of a multidrug-resistant (MDR) murine erythroleukemia cell line with daunomycin (DNM) in combination with lacidipine (LCD) or josamycin (JSM).
- Comparison of MDR reversal activity with verapamil (VRP) and erythromycin (ERY).
- Measurement of daunomycin (DNM) accumulation in treated cells.
Main Results:
- LCD and JSM demonstrated superior MDR reversal activity compared to VRP and ERY, respectively.
- Daunomycin (DNM) accumulation in resistant cells treated with LCD or JSM was comparable to that in parental cells.
- Lacidipine (LCD) reversed MDR at low concentrations without altering DNM accumulation.
Conclusions:
- Lacidipine (LCD) and josamycin (JSM) are effective modulators for overcoming MDR in this cell line.
- The mechanism of MDR reversal by LCD may involve factors other than P-glycoprotein (P-170) mediated drug efflux.
- These findings suggest potential for novel combination therapies to improve cancer treatment outcomes.