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Aspergillus species strain m39 produces two naphtho‐γ‐pyrones that reverse drug resistance in human KB cells
Author(s) -
Ikeda ShunIchi,
Sugita Masanori,
Yoshimura Akihiko,
Sumizawa Tomoyuki,
Douzono Haruhiko,
Nagata Yukihiro,
Akiyama ShinIchi
Publication year - 1990
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910450323
Subject(s) - efflux , biology , vinblastine , aspergillus , drug resistance , p glycoprotein , microbiology and biotechnology , multiple drug resistance , strain (injury) , biochemistry , genetics , chemotherapy , anatomy
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 3 H‐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.