ENHANCEMENT OF DRUG ACCUMULATION BY ANDRASTIN-A PRODUCED BY PENICILLIUM SP. FO-3929 IN VINCRISTINE-RESISTANT KB CELLS

In the course of our screening for compounds that reverse multidrug re sistance, we found that the cytotoxicity of vincristine was enhanced 1 .5 similar to 20-fold depending on the concentration of andrastin A in vincristine-resistant KB cells (VJ-300), Andrastin A alone had no eff ect on the growth of drug sensitive KB cells and VJ-300 cells. On the other hand, andrastin A (25 and 50 mu g/ml) significantly enhanced acc umulation of [H-3]vincristine in VJ-300 cells. Andrastin A (50 mu g/ml ) completely inhibited the binding of [H-3]azidopine to the P-glycopro tein in VJ-300 cells. The result suggests that andrastin A directly in teracts with P-glycoprotein and inhibits the efflux of antitumor agent s in drug resistant cells.