title: The photodynamic effect of far-red range phthalocyanines (AlPc and Pc green) supported by electropermeabilization in human gastric adenocarcinoma cells of sensitive and resistant type.
abstract: BACKGROUND
  Electroporation (EP) is commonly applied for effective drug transport thorough cell membranes based on the application of electromagnetic field. When applied with cytostatics, it is called electrochemotherapy (ECT) - a quite new method of cancer treatment. A high-voltage pulse causes the formation of temporary pores in the cell membrane which create an additional way for the intracellular drug transport. In the current work, EP was effectively merged with the already known photodynamic therapy (PDT) to selective photosensitizers' delivery to diseased tissue. The application of electroporation can reduce the dose of applied drug.
  
  
  OBJECTIVE
  The aim of research was to evaluate the effectiveness of photodynamic reaction using two near infrared cyanines (AlPc and Pc green) combined with electroporation in two human gastric adenocarcinoma cell lines.
  
  
  METHODS
  Two human cell lines - EPG85-257P (parental) and EPG85-257RDB (resistant to daunorubicin) - of gastric cancer were used. The effect of two photosensitizers (aluminum 1,8,15,22-tetrakis(-phenylthio)-29H,31H-phthalocyanine chloride and Phthalocyanine green) was investigated. The efficiency of EP parameters was assessed by propidium iodide uptake. The viability assay was applied to analyse EP, PDT and EP-PDT effect. Cyanine localization was determined by confocal microscopy. Immunocytochemical evaluation of manganese superoxide dismutase and glutathione S-transferase-pi was determined after applied therapies.
  
  
  RESULTS
  PDT in combination with EP affected the viability of EPG85-257P and EPG85-257RDB cells negatively while both cyanine were used. The most evident changes were observed in the following concentrations: 15, 10 and 5μM. The optimal field strength for enhanced EP-PDT was 800 and 1200V/cm. AlPc distributed selectively in the lysosomes of parental cell line.
  
  
  CONCLUSIONS
  PDT, enhanced by EP, caused decreased viability when compared to the application of PDT alone. Both phthalocyanines found to be more effective after electroporation. Due to the low concentration of light-sensitive compounds and safety of electroporation itself, a treatment plan can be an alternative therapeutic modality against gastric adenocarcinomas.
authors: Department of General Zoology, Zoological Institute, University of Wroclaw, Sienkiewicza 21Street, 50-335 Wroclaw, Poland.
authors: Anna
authors: A
authors: Zielichowska
authors: Department of Medical Biochemistry, Medical University, Chalubinskiego 10Street, 50-368 Wroclaw, Poland.
authors: Jolanta
authors: J
authors: Saczko
authors: Department of General Zoology, Zoological Institute, University of Wroclaw, Sienkiewicza 21Street, 50-335 Wroclaw, Poland.
authors: Arnold
authors: A
authors: Garbiec
authors: Department of General Zoology, Zoological Institute, University of Wroclaw, Sienkiewicza 21Street, 50-335 Wroclaw, Poland.
authors: Magda
authors: M
authors: Dubińska-Magiera
authors: Institute of Immunology and Experimental Therapy Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland.
authors: Joanna
authors: J
authors: Rossowska
authors: Department of Histology and Embryology, Medical University, Chałubińskiego 6a, 50-367 Wrocław, Poland.
authors: Paweł
authors: P
authors: Surowiak
authors: Department of Medical Biochemistry, Medical University, Chalubinskiego 10Street, 50-368 Wroclaw, Poland.
authors: Anna
authors: A
authors: Choromańska
authors: Department of General Zoology, Zoological Institute, University of Wroclaw, Sienkiewicza 21Street, 50-335 Wroclaw, Poland.
authors: Małgorzata
authors: M
authors: Daczewska
authors: Department of Medical Biochemistry, Medical University, Chalubinskiego 10Street, 50-368 Wroclaw, Poland. Electronic address: julita.kulbacka@am.wroc.pl.
authors: Julita
authors: J
authors: Kulbacka
authors: Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany.
authors: Hermann
authors: H
authors: Lage
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004560:Electricity; D018274:Electroporation; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008027:Light; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D011419:Propidium / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011419:Propidium; C060570:aluminum phthalocyanine; C505810:phthalocyanine green; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D003630:Daunorubicin
keywords: Electroporation; Gastric adenocarcinoma; Photodynamic reaction; Phthalocyanines