title: Cell specific effects of polyunsaturated fatty acids on 5-aminolevulinic acid based photosensitization.
abstract: 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.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gt. 3, N-7489, Trondheim, Norway. odrun.gederaas@medisin.ntnu.no
authors.forename: Odrun Arna
authors.initials: OA
authors.lastname: Gederaas
authors.forename: Svanhild Arentz
authors.initials: SA
authors.lastname: Schønberg
authors.forename: Ståle
authors.initials: S
authors.lastname: Ramstad
authors.forename: Kristian
authors.initials: K
authors.lastname: Berg
authors.forename: Anders
authors.initials: A
authors.lastname: Johnsson
authors.forename: Hans E
authors.initials: HE
authors.lastname: Krokan
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D005231:Fatty Acids, Unsaturated; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D008315:Malondialdehyde; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D024502:alpha-Tocopherol