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 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.
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The Kitasato Institute and School of Pharmaceutical Sciences, The Kitasato University, Tokyo, Japan.
Hayashi
M
M
Fukami
A
A
Obata
R
R
Sunazuka
T
T
Tomoda
H
H
Komiyama
K
K
Omura
S
S
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*
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