title: Reversal of ABCB1-related Multidrug Resistance of Colonic Adenocarcinoma Cells by Phenothiazines.
abstract: BACKGROUND
  The most common mechanism that reduces the efficacy of anticancer agents is overexpression of ATP-binding cassette (ABC) drug transporters. Phenothiazines and structurally-related compounds can sensitize multidrug-resistant (MDR) cells to chemotherapeutics.
  
  
  METHODS
  Phenothiazine derivatives were investigated regarding their anticancer and MDR-reversing effect on colonic adenocarcinoma cells. The anti-proliferative and cytotoxic effects of the derivatives were assessed by the thiazolyl blue tetrazolium bromide (MTT) method, the modulation of the ABCB1 activity was measured by rhodamine 123 accumulation assay using flow cytometry.
  
  
  RESULTS
  All phenothiazines exhibited potent cytotoxic effect on the sensitive and MDR colon adenocarcinoma cell lines. The inhibition of the ABCB1 transporter was greater in the presence of the phenothiazine derivatives than for the known ABCB1 inhibitor verapamil.
  
  
  CONCLUSIONS
  It can be concluded that these derivatives show synergism in the presence of doxorubicin and could have potential as ABCB1 inhibitors.
authors.affiliation: Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Daniella
authors.initials: D
authors.lastname: Takács
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Csonka
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Horváth
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Tímea
authors.initials: T
authors.lastname: Windt
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Márió
authors.initials: M
authors.lastname: Gajdács
authors.affiliation: Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Riedl
authors.affiliation: Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Hajós
authors.affiliation: Unit of Travel Medicine, Center of Malaria and Other Tropical Diseases, Institute of Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Molnár
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary spengler.gabriella@med.u-szeged.hu.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000235:genetics; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D010640:Phenothiazines / Q000008:administration & dosage; D020112:Rhodamine 123 / Q000008:administration & dosage; D014700:Verapamil / Q000008:administration & dosage
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010640:Phenothiazines; D020112:Rhodamine 123; D004317:Doxorubicin; D014700:Verapamil
keywords: MDR; P-glycoprotein (ABCB1); Phenothiazines; apoptosis; colon adenocarcinoma; doxorubicin; multidrug resistance; rhodamine 123; verapamil