title: Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis.
abstract: BACKGROUND
  Hydantoin derivatives are very promising candidates to improve the efficacy of anticancer chemotherapy. Previously, we demonstrated that eight hydantoin derivatives inhibited the P-glycoprotein (ABCB1) efflux pump of mouse T-lymphoma cells, as well as acting synergistically with the anticancer drug doxorubicin.
  
  
  METHODS
  The activity of the hydantoin derivatives were investigated in another MDR cancer model, namely Colo 205/S sensitive and Colo 320/R resistant colon carcinoma cells respectively, having normal or overexpressed ABCB1 systems.
  
  
  RESULTS
  Among the hydantoin derivatives evaluated, BS-1, MN-3 and JH-63 were the most effective ABCB1 transporter inhibitors at the concentration of 4 mg/l on the Colo 320/R cells, compared to the positive control, verapamil.
  
  
  CONCLUSIONS
  The derivatives did not induce apoptosis of Colo 320/R resistant colon carcinoma cells, indicating that these hydantoin compounds are potent efflux pump inhibitors (EPI) without affecting the signalling pathways that regulate apoptosis.
authors.affiliation: Institute of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary. gspengler@ihmt.unl.pt
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Handzlik
authors.forename: Imre
authors.initials: I
authors.lastname: Ocsovszki
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kiec-Kononowicz
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnar
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D006827:Hydantoins / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D020112:Rhodamine 123 / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006827:Hydantoins; D020112:Rhodamine 123