The antiprogestatin drug RU 486 potentiates doxorubicin cytotoxicity in multidrug resistant cells through inhibition of P-glycoprotein function.
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Lecureur V, Fardel O, Guillouzo A
The antiprogestatin drug RU 486 potentiates doxorubicin cytotoxicity in multidrug resistant cells through inhibition of P-glycoprotein function.
FEBS Lett. 1994 Nov 28;355(2):187-91.
- PubMed ID
- 7982498 [ View in PubMed]
- Abstract
The antiprogestatin drug RU 486 was examined for its effect on doxorubicin cellular retention and cytotoxicity in multidrug resistant cells overexpressing P-glycoprotein (P-gp). RU 486 was shown to strongly enhance intracellular accumulation of doxorubicin in both rat hepatoma RHC1 and human leukemia K562 R7 drug-resistant cells but had no action in SDVI drug-sensitive liver cells. The antiprogestatin drug when used at 10 microM, a concentration close to plasma concentrations achievable in humans, was able to hugely increase the sensitivity of RHC1 cells to doxorubicin. RU 486 appeared to prevent the P-gp-mediated doxorubicin efflux out of RHC1 cells and was demonstrated to interfere directly with P-gp drug binding sites since it blocked P-gp labelling by the photoactivable P-gp ligand azidopine. These results thus demonstrate that RU 486 can downmodulate anticancer drug resistance through inhibition of P-gp function.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Mifepristone P-glycoprotein 1 Protein Humans UnknownInhibitorInducerDetails