Phototoxic effect of photodynamic therapy on lung cancer cells grown as a monolayer and three dimensional multicellular spheroids

Lasers Surg Med. 2013 Mar;45(3):186-94. doi: 10.1002/lsm.22121. Epub 2013 Mar 4.

Abstract

Background and 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.

Materials and 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.

Conclusion: 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Indoles / pharmacology*
  • Microscopy, Fluorescence
  • Organometallic Compounds / pharmacology*
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Spheroids, Cellular / drug effects*
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Indoles
  • Organometallic Compounds
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • zinc(II) phthalocyanine trisulfonic acid