Sensitization of Chronic Myeloid Leukemia Cells to Adriamycin Cytotoxicity by Clofibrate

Clofibrate (CPIB), an antihyperlipidemic agent, was employed as a drug response modulator in this study to evaluate its action, if any, on adriamycin (ADR) cytotoxicity in adriamycin insensitive chronic myeloid leukemia (CML) cells in vitro. Inhibition of (3H)-thymidine incorporation was used as a measure of DNA biosynthesis inhibition. A marginally toxic concentration of CPIB [0.001% (v/v)] was utilized to evaluate the cytotoxicity in CML cells exposed to ADR 5 and 10 micrograms/ml. A heterogeneous response was observed in 16 different CML blood samples, 9 samples displaying a synergistic, 3 an additive and 4 a less than additive inhibition of DNA biosynthesis when exposed to the combination of ADR and CPIB. The cytotoxic effect induced by ADR alone and in combination with CPIB was found to be irreversible. The data suggest that the cell membrane modulating drug CPIB is effective as an adjuvant to enhance the antiproliferative action of ADR.