Enhancement of drug accumulation by andrastin A produced by Penicillium sp. FO-3929 in vincristine-resistant KB cells.
In the course of our screening for compounds that reverse multidrug resistance, we found that the cytotoxicity of vincristine was enhanced 1.5-20-fold depending on the concentration of andrastin A in vincristine-resistant KB cells (VJ-300). Andrastin A alone had no effect on the growth of drug sensitive KB cells and VJ-300 cells. On the other hand, andrastin A (25 and 50 micrograms/ml) significantly enhanced accumulation of [3H]vincristine in VJ-300 cells. Andrastin A (50 micrograms/ml) completely inhibited the binding of [3H]azidopine to the P-glycoprotein in VJ-300 cells. The result suggests that andrastin A directly interacts with P-glycoprotein and inhibits the efflux of antitumor agents in drug resistant cells.
Rho
M C
MC
Kitasato Institute, Tokyo, Japan.
Toyoshima
M
M
Hayashi
M
M
Uchida
R
R
Shiomi
K
K
Komiyama
K
K
Omura
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects; D000345:Affinity Labels; D000730:Androstadienes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001386:Azides; D004095:Dihydropyridines; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D010407:Penicillium / Q000737:chemistry*; D014750:Vincristine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D000730:Androstadienes; D000972:Antineoplastic Agents, Phytogenic; D001386:Azides; D004095:Dihydropyridines; D004791:Enzyme Inhibitors; C100395:andrastin A; D014750:Vincristine; C041130:azidopine