title: The influence of phenothiazine derivatives on intracellular accumulation of cationic cyanine dye DiOC6(3) in LoVo-DX cells.
abstract: OBJECTIVE
  This study aimed to evaluate the influence of phenothiazine derivatives (PDs) on the intracellular accumulation of cyanine dye DiOC6(3) in doxorubicin-resistant LoVo-DX cell line, with overexpression of P-glycoprotein.
  
  
  METHODS
  In order to maintain a high expression level of P-gp, the LoVo-DX cells were grown in the presence of doxorubicin (100 ng/ml). The time-dependent fluorescence signal (T-DFS) of the intracellular accumulation of DiOC6(3), in the presence of PDs, was then recorded. The rate constants k1, k2, k3 and amplitudes of T-DFS, describing the intracellular accumulation process, were determined based on the respective theoretical equation.
  
  
  RESULTS
  The values of k1 and k2 were dependent on the hydrophobicity (logP) of the PDs used as drug resistance modulators. A rise of k1 and k2 values was observed when the logP of PDs increased.
  
  
  CONCLUSIONS
  We suggest that the k1 and k2 rate constants could be regarded as useful parameters for assessment of PDs as well as of other compounds of potential application as reversers of multidrug resistance.
authors.affiliation: Department of Biophysics, Wrocław Medical University, ul. Chałubińskiego 9, 50-368 Wrocław, Poland. andrzej.pola@am.wroc.pl
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pola
authors.forename: Daniela
authors.initials: D
authors.lastname: Mosiadz
authors.forename: Jolanta
authors.initials: J
authors.lastname: Saczko
authors.forename: Teresa
authors.initials: T
authors.lastname: Modrzycka
authors.forename: Krystyna
authors.initials: K
authors.lastname: Michalak
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D002232:Carbocyanines / Q000493:pharmacokinetics*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D018613:Microscopy, Confocal; D010640:Phenothiazines / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002232:Carbocyanines; D005456:Fluorescent Dyes; D010640:Phenothiazines; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine; D004317:Doxorubicin