Reversal of multidrug resistance by 7-O-benzoylpyripyropene A in multidrug-resistant tumor cells

7-O-Benzoylpyripyropene A (7-O-BzP), a semi-synthetic analog of pyripyropen e, was investigated for its reversing effect on multidrug-resistant (MDR) t umor cells. 7-O-BzP (6.25 mug/ml) completely reversed resistance against vi ncristine and adriamycin in vincristine-resistant KB cells (VJ-300) and adr iamycin-resistant P388 cells (P388/ADR), respectively. 7-O-BzP alone had no effect on the growth of drug sensitive and drug-resistant cells. 7-O-BzP ( 6.25 mug/ml) significantly enhanced accumulation of [H-3]vincristine in VJ- 300 cells and completely inhibited the binding of [H-3]azidopine to the P-g lycoprotein in VJ-300 cells and P388/ADR cells. The result suggests that 7- O-BzP effectively reverses P-glycoprotein-related MDR by interacting direct ly with P-glycoprotein in drug resistant VJ-300 and P388/ADR cells.