Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla
Résumé
Bio-guided fractionation of the roots of Paris polyphylla (Trilliaceae), based on inhibition of P-glycoprotein-mediated daunorubicin efflux in K562/R7 cell line, led to isolation and identification of the three saponins 3-O-Rha(12)[Ara(14)]Glc-pennogenine, gracillin and polyphyllin D, and the two ecdysteroids 20-hydroxyecdysone and pinnatasterone. These compounds were tested for multidrug reversion on P-glycoprotein (ABCB1) with both drug-selected and transfected cell lines, and also on Breast Cancer Resistance Protein (BCRP/ABCG2). By contrast to a weak efficiency on BCRP, the three saponins displayed significant effects as inhibitors of P-glycoprotein-mediated drug efflux.
Mots clés
Rhizome
Saponins
Spirostans
Steroids
Humans
Drug Resistance
Multiple
Leukemia
Angiosperms
ATP-Binding Cassette Transporters
Cyclosporine
Daunorubicin
Diosgenin
Ecdysteroids
Ecdysterone
Immunosuppressive Agents
K562 Cells
Membrane Transport Modulators
Multidrug Resistance-Associated Proteins
Neoplasm
Neoplasm Proteins
P-Glycoprotein
Plant Extracts