title: Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I meningioma cells corresponds to ferrochelatase activity.
abstract: 5-Aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PpIX), which can be used as a photosensitizer in photodynamic therapy (PDT). Accumulation of PpIX in benign meningioma cells has been observed previously, its exploitation for PDT, however, was discouraged by inconsistent results. To evaluate PDT for benign meningiomas, we investigated PpIX synthesis in two human meningioma cell lines (HBL-52 and BEN-MEN-1), their respective extracellular loss of PpIX and corresponding ferrochelatase (FECH) activity as well as their susceptibility to PDT. We demonstrated PpIX production after 5-ALA administration and minor loss to the extracellular space in both cell lines. However, significantly more (up to five times) PpIX was accumulated in BEN-MEN-1 as compared with HBL-52 cells. FECH activity was 2.7-fold higher in HBL-52 compared with BEN-MEN-1 cells and accordingly higher FECH levels could be shown in HBL-52 cells by Western blot analysis. BEN-MEN-1 cells were much more sensitive to PDT and cells could be almost completely killed by irradiation doses of 2 J cm(-2) , whereas HBL-52 showed only an insufficient response at this irradiation dose. We conclude that differences in intracellular PpIX concentrations between HBL-52 and BEN-MEN-1 benign meningioma cells were mainly due to differences in FECH activity and that these differences correspond to their susceptibility to 5-ALA-induced PDT.
authors.affiliation: Department of Neurosurgery, University Hospital Schleswig Holstein, Campus Kiel, Germany. hefti.oser@bluewin.ch
authors.forename: Martin
authors.initials: M
authors.lastname: Hefti
authors.forename: Fabian
authors.initials: F
authors.lastname: Holenstein
authors.forename: Ina
authors.initials: I
authors.lastname: Albert
authors.forename: Herbert
authors.initials: H
authors.lastname: Looser
authors.forename: Vera
authors.initials: V
authors.lastname: Luginbuehl
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005294:Ferrochelatase / Q000378:metabolism*; D006801:Humans; D008577:Meningeal Neoplasms / Q000201:enzymology / Q000473:pathology*; D008579:Meningioma / Q000201:enzymology / Q000473:pathology*; D017319:Photosensitizing Agents / Q000494:pharmacology*
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; D005294:Ferrochelatase