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

M. C. Rho, M. Hayashi, A. Fukami, R. Obata, T. Sunazuka, H. Tomoda, K. Komiyama, S. Omura

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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 μg/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 μg/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.

Original languageEnglish
Pages (from-to)1201-1206
Number of pages6
JournalJournal of Antibiotics
Volume53
Issue number10
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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