Effects of cytochalasins and colchicine on the accumulation and retention of daunomycin and vincristine in drug resistant tumor cells

Abstract

Cytochalasin B and D enhanced vincristine (VCR) and daunomycin (DAU) accumulation in tumor cells, especially in VCR- and DAU-resistant cell lines. The effect of cytochalasin B, and to a lesser extent cytochalasin D, was almost equivalent to that observed for verapamil, a calcium channel blocker which has been reported to enhance drug accumulation in tumor cells. Cytochalasin B was most effective in VCR- and DAU-sensitive cells; however, the effect in resistant cells was less than that observed for verapamil, suggesting a different mode of action between these drugs in sensitive and resistant cells. Enhanced accumulation of VCR and DAU by cytochalasins was mediated by the inhibition of outward transport of VCR and DAU from tumor cells. Colchicine had no effect on VCR and DAU accumulation. Cytochalasins, especially cytochalasin D is a specific inhibitor of microfilament assembly in cells. These results indicate that the cellular microfilament system plays a prominent role in drug transport of tumor cells, and that an intact microtubular system is less involved.