title: Phototoxic effect of photodynamic therapy on lung cancer cells grown as a monolayer and three dimensional multicellular spheroids.
abstract: OBJECTIVE
  Photodynamic therapy (PDT) is a minimally invasive therapeutic modality for the treatment of neoplastic and non-neoplastic diseases. The photochemical interaction of light, photosensitizer (PS) and molecular oxygen produces singlet oxygen which induces cell death. The effectiveness of zinc sulfophthalocyanine (ZnPcSmix ) has been shown on A549 monolayers and not on MCTS. The objective of this study was to investigate whether the same pattern of cell death would be induced in lung cancer cells (A549) grown as monolayer cells compared to three dimensional multicellular tumor spheroids (MCTS) using the same laser parameters.
  
  
  METHODS
  Commercially purchased A549 cells used in this study were cultured as monolayers and as MCTS. ZnPcSmix at different concentrations [0, 5, 10, 20, and 40 µM] was used and activated at a wavelength of 680 nm with 5 J/cm2. Lysosomal and mitochondrial damage after PDT and reactive oxygen species (ROS) production were determined by fluorescent microscopy. Changes in cellular responses were evaluated using cell morphology, viability, proliferation, cytotoxicity, and cell death analysis.
  
  
  RESULTS
  Cells exposed to neither laser light nor PS, showed no changes in cell morphology, proliferation, cytotoxicity, and ROS production. However, cells treated with light activated ZnPcSmix resulted in a significant production of ROS and a dose dependant decrease in viability and proliferation as well as an increase in cell membrane damage in both monolayer and MCTSs.
  
  
  CONCLUSIONS
  ZnPcSmix PS used in this study induced damage to vital organelles and was effective in inducing apoptosis in lung cancer cells grown as a monolayer and MTCS through ROS production.
authors: Faculty of Health Sciences, Laser Research Centre, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa.
authors: Sello L
authors: SL
authors: Manoto
authors: Nicolette N
authors: NN
authors: Houreld
authors: Heidi
authors: H
authors: Abrahamse
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C063072:zinc(II) phthalocyanine trisulfonic acid