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: M C Rho, M Hayashi, A Fukami, R Obata, T Sunazuka, H Tomoda, K Komiyama, S Omura
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 53 Issue 10 Pg. 1201-6 (Oct 2000) ISSN: 0021-8820 [Print] England
• PMID: 11132967 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 7-O-benzoylpyripyropene A
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Azides
• Dihydropyridines
• Pyridones
• Sesquiterpenes
• Vincristine
• azidopine
• Doxorubicin

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Antineoplastic Agents (pharmacology)
• Azides (metabolism)
• Carcinoma, Squamous Cell
• Dihydropyridines (metabolism)
• Doxorubicin (pharmacology)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Humans
• KB Cells
• Pyridones (pharmacology)
• Sesquiterpenes (pharmacology)
• Tumor Cells, Cultured
• Vincristine (metabolism, pharmacology)