title: Photodynamic responsiveness of human leukemia Jurkat/A4 cells with multidrug resistant phenotype.
abstract: Photodynamic therapy (PDT) is considered as a possible alternative approach to overcoming multidrug resistance (MDR). Analysis of cross-resistance to PDT in cells with different MDR pathways and resistance levels seems to be advantageous for elucidating the general mechanisms of cancer cell resistance to various treatment modalities.
  
  
  OBJECTIVE
  The aim of the study was to clarify whether the Jurkat/A4 leukemia cells with MDR phenotype are cross-resistant to PDT.
  
  
  METHODS
  Human T-cell acute lymphoblastic leukemia line Jurkat and Jurkat/A4 subline with MDR phenotype were used. 5-Aminolevulinic acid (ALA) and Photolon (a complex of chlorine-e6 and polyvinylpyrrolidone; PL) or gold nanocomposite of PL were applied as photosensitizers. The cells were pretreated with photosensitizers and exposed to laser radiation at corresponding wavelengths. The phototoxicity was assessed in trypan blue exclusion test. The hypodiploid cell fraction was analyzed by flow cytometry of propidium iodide-stained cells. Expression of genes related to PDT resistance was analyzed by microarray technique with Affymetrix U133A chips.
  
  
  RESULTS
  ALA-mediated PDT resulted in dose-dependent cell death in both lines, the relative photodynamic efficacy in Jurkat/A4 cells being inferior to that in the parental Jurkat cells. There was no correlation between phototoxicity and apoptosis induction both in Jurkat and Jurkat/A4 cells. PL-mediated general phototoxicity in Jurkat cells amounted up to 75% at the maximal photosensitizer dose with about 40% of apoptotic death fraction. PL-phototoxicity in Jurkat/A4 cells was considerably lower. In contrast to Jurkat cells, PL-gold composite did not increase the efficacy of photosensitization as compared to free PL in Jurkat/A4 cells.
  
  
  CONCLUSIONS
  Multidrug-resistant Jurkat/A4 cells exhibit reduced sensitivity to phototoxic effect in comparison with parental Jurkat cells independently of nature of the photosensitizer being assayed.
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv 03022, Ukraine.
authors.forename: A A
authors.initials: AA
authors.lastname: Philchenkov
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv 03022, Ukraine.
authors.forename: E D
authors.initials: ED
authors.lastname: Shishko
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv 03022, Ukraine.
authors.forename: M P
authors.initials: MP
authors.lastname: Zavelevich
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv 03022, Ukraine.
authors.forename: L M
authors.initials: LM
authors.lastname: Kuiava
authors.affiliation: Miyagi Cancer Center 47-1 Nodayama, Shiote, Medeshima, Natori, Miyagi 981-1293, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.affiliation: N.N. Blokhin Cancer Research Center, Moscow 115478, Russian Federation.
authors.forename: D Y
authors.initials: DY
authors.lastname: Blokhin
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv 03022, Ukraine.
authors.forename: I O
authors.initials: IO
authors.lastname: Shton
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv 03022, Ukraine.
authors.forename: N F
authors.initials: NF
authors.lastname: Gamaleia
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D010641:Phenotype; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology
chemical_list: D017319:Photosensitizing Agents