Cell specific effects of polyunsaturated fatty acids on 5-aminolevulinic acid based photosensitization

Photochem Photobiol Sci. 2005 Apr;4(4):383-9. doi: 10.1039/b502000j. Epub 2005 Mar 8.


The purpose of this study was to examine whether the dietary components n-6 and n-3 polyunsaturated fatty acids (PUFAs) may potentiate the effect of photodynamic therapy (PDT) in human cancer cell lines by enhancing the lipid peroxidation. The effects of the porphyrin precursor 5-aminolevulinic acid (5-ALA) and light (320 < lambda < 440 nm, 33 W m(-2)), with or without docosahexaenoic acid (DHA) or arachidonic acid (AA), were tested in the colon carcinoma cell lines SW480 and WiDr, the glioblastoma cell line A-172 and the lung adenocarcinoma cell line A-427. The production of endogenous protoporphyrin IX (PpIX) varied substantially between the cell lines and was approximately 4-fold higher in WiDr as compared with SW480. Cell killing by 5-ALA-PDT also varied between the cell lines, but without clear correlation with PpIX levels. Treatment with DHA or AA (10 or 70 microM, 48 or 72 h) in combination with 5-ALA-PDT (1 or 2 mM) enhanced the cytotoxic effect in A-172 and A-427 cells, but not in SW480 and WiDr cells. While 5-ALA-PDT alone increased the lipid peroxidation in A-172 and WiDr cells only, 5-ALA-PDT plus PUFAs increased the lipid peroxidation substantially in all four cell lines. Interestingly, alpha-tocopherol (50 microM, 48 h) strongly reduced lipid peroxidation after all treatments in all cell lines, while cytotoxicity was only reduced substantially in A-427 cells. This demonstrates that induction of lipid peroxidation is not a general mechanism responsible for the cytotoxicity of 5-ALA-PDT, although it may be important in cell lines with an inherent sensitivity to lipid peroxidation products. Thus, the mechanisms of cell growth inhibition/cell killing by PDT are complex and cell specific.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / pharmacology*
  • Arachidonic Acid / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Docosahexaenoic Acids / pharmacology
  • Fatty Acids, Unsaturated / pharmacology*
  • Humans
  • Malondialdehyde / metabolism
  • Photochemotherapy / methods*
  • Photosensitizing Agents / metabolism
  • Protoporphyrins / metabolism
  • alpha-Tocopherol / pharmacology


  • Fatty Acids, Unsaturated
  • Photosensitizing Agents
  • Protoporphyrins
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Malondialdehyde
  • Aminolevulinic Acid
  • protoporphyrin IX
  • alpha-Tocopherol