Aspergillus species strain m39 produces two naphtho‐γ‐pyrones that reverse drug resistance in human KB cells

Shun‐Ichi ‐I Ikeda, Masanori Sugita, Akihiko Yoshimura, Tomoyuki Sumizawa, Haruhiko Douzono, Yukihiro Nagata, Shin‐Ichi ‐I Akiyama

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26 Citations (Scopus)

Abstract

One thousand fungi and Actinomycetes were investigated to see whether they produced compounds that reverse multidrug resistance in KB cells. Only one Aspergillus strain M39 produced agents with resistance‐reversing activity and these compounds were identified to be rubrofusarin B and dianhydro‐aurasperone C. Rubrofusarin B only slightly reversed the resistance of KB‐C2 cells to Adriamycin and daunomycin, partially reversed the resistance to chromomycin A3, and almost completely reversed the resistance to vincristine and mitomycin C. Purified dianhydro‐aurasperone C and rubrofusarin B had similar effects on drug resistance in KB‐8‐5 cells. Dianhydro‐aurasperone C enhanced the accumulation of vinblastine in KB‐8‐5 cells and inhibited the efflux of vinblastine from the cells. Dianhydro‐aurasperone C and rubrofusarin B at 10 μ M completely inhibited 3H‐azidopine photolabelling of P‐glycoprotein. The two products of Aspergillus strain M39 appear to reverse multi‐drug resistance by interacting with P‐glycoprotein and inhibiting its role as an active efflux pump.

Original languageEnglish
Pages (from-to)508-513
Number of pages6
JournalInternational Journal of Cancer
Volume45
Issue number3
DOIs
Publication statusPublished - 1990 Mar 15
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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