title: Reversal of multidrug resistance by 7-O-benzoylpyripyropene A in multidrug-resistant tumor cells.
abstract: 7-O-Benzoylpyripyropene A (7-O-BzP), a semi-synthetic analog of pyripyropene, was investigated for its reversing effect on multidrug-resistant (MDR) tumor cells. 7-O-BzP (6.25 microg/ml) completely reversed resistance against vincristine and adriamycin in vincristine-resistant KB cells (VJ-300) and adriamycin-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 microg/ml) significantly enhanced accumulation of [3H]vincristine in VJ-300 cells and completely inhibited the binding of [3H]azidopine to the P-glycoprotein in VJ-300 cells and P388/ADR cells. The result suggests that 7-O-BzP effectively reverses P-glycoprotein-related MDR by interacting directly with P-glycoprotein in drug resistant VJ-300 and P388/ADR cells.
authors.affiliation: The Kitasato Institute and School of Pharmaceutical Sciences, The Kitasato University, Tokyo, Japan.
authors.forename: M C
authors.initials: MC
authors.lastname: Rho
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: A
authors.initials: A
authors.lastname: Fukami
authors.forename: R
authors.initials: R
authors.lastname: Obata
authors.forename: T
authors.initials: T
authors.lastname: Sunazuka
authors.forename: H
authors.initials: H
authors.lastname: Tomoda
authors.forename: K
authors.initials: K
authors.lastname: Komiyama
authors.forename: S
authors.initials: S
authors.lastname: Omura
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001386:Azides / Q000378:metabolism; D002294:Carcinoma, Squamous Cell; D004095:Dihydropyridines / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007624:KB Cells; D011728:Pyridones / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C418200:7-O-benzoylpyripyropene A; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001386:Azides; D004095:Dihydropyridines; D011728:Pyridones; D012717:Sesquiterpenes; D014750:Vincristine; C041130:azidopine; D004317:Doxorubicin