title: Multidrug resistance reversing activity of newly developed phenothiazines on P-glycoprotein (ABCB1)-related resistance of mouse T-lymphoma cells.
abstract: BACKGROUND
  Phenothiazines have anticancer properties and are able to reverse the multidrug resistance of neoplastic cells by inhibiting the ATP-binding cassette, sub-family B (MDR/TAP), member 1 protein (ABCB1 or P-glycoprotein) activity.
  
  
  METHODS
  A series of new phenothiazine derivatives was investigated regarding their ABCB1-modulating effect on multidrug resistant mouse T-lymphoma cells by rhodamine 123 accumulation assay and real-time ethidium bromide accumulation assay.
  
  
  RESULTS
  The phenothiazine derivatives exhibited a potent anticancer effect on the parental cell line and on its multidrug-resistant mouse T-lymphoma subline overexpressing the ABCB1 transporter. The inhibition of the ABCB1 transporter in the presence of the newly-developed phenothiazines was greater than that for the known ABCB1 inhibitors thioridazine and verapamil.
  
  
  CONCLUSIONS
  Based on the chemical structures and biological activity, compounds with bivalent sulfur atom in the phenothiazine ring demonstrated marked ABCB1-modulating effect, however, other derivatives with halogen or amide substitutions were ineffective.
authors.affiliation: Institute of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary. spengler.gabriella@med.u-szeged.hu.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Daniella
authors.initials: D
authors.lastname: Takács
authors.forename: Adám
authors.initials: A
authors.lastname: Horváth
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Riedl
authors.forename: György
authors.initials: G
authors.lastname: Hajós
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
authors.forename: József
authors.initials: J
authors.lastname: Molnár
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010640:Phenothiazines / Q000737:chemistry / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D010640:Phenothiazines; D020112:Rhodamine 123; C031637:phenothiazine
keywords: ABCB1; ATP-binding cassette protein B1; P-glycoprotein; Phenothiazines; ethidium bromide; mouse T-lymphoma cell lines; multidrug resistance; rhodamine 123; thioridazine; verapamil