title: Reversion of the P-glycoprotein-mediated multidrug resistance of cancer cells by FK-506 derivatives.
abstract: FK-506 is a resistance-modulating agent (RMA) for tumor cells whose multidrug resistance (MDR) involves a P-glycoprotein (Pgp)-mediated anti-cancer drug efflux. The family of FK-506 relatives and derivatives includes analogs which display a whole range of chemosensitizing strengths, from no detectable RMA activity to a complete reversion of the MDR phenotype. Similarly, FK-506 analogs display a whole range of immunosuppressive activities, including inactive ones. FK-506 was compared for RMA activity with 11 FK-506 analogs which were at least 20-fold less active than FK-506 for the inhibition of the bi-directional mixed lymphocyte reaction displayed the whole range of RMA activity. One such strong RMA derivative of FK-506 (SDZ 280-629) was further shown able to restore completely daunomycin retention by highly resistant MDR P388 tumor cells.
authors.affiliation: Preclinical Research, Sandoz Pharma Ltd, Basel, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Jachez
authors.forename: D
authors.initials: D
authors.lastname: Boesch
authors.forename: M A
authors.initials: MA
authors.lastname: Grassberger
authors.forename: F
authors.initials: F
authors.lastname: Loor
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells; D002352:Carrier Proteins / Q000502:physiology*; D003078:Colchicine / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D007941:Leukemia P388; D008562:Membrane Glycoproteins / Q000502:physiology*; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D004317:Doxorubicin; D003078:Colchicine; D016559:Tacrolimus; D003630:Daunorubicin