Susceptibility to 5-Aminolevulinic acid based Photodynamic Therapy in WHO I Meningioma cells Corresponds to Ferrochelatase Activity
Albert, Ina; ; (2011). Susceptibility to 5-Aminolevulinic acid based Photodynamic Therapy in WHO I Meningioma cells Corresponds to Ferrochelatase Activity. Photochemistry and Photobiology, 87(1): 235 - 241. Peer reviewed.; ;
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 two five times) PpIX was accumulated in BEN-MEN-1 as compared to HBL-52 cells. FECH activity was 2.7 fold higher in HBL-52 compared to 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 insuffient
response at this irradiation dose. We conclude that differences in intracellular PpIX concentrations between HBL-52 and BEN-MEN-1 benign menigioma cells were mainly due to differences in FECH activity and that these differences correspond to their susceptibility to 5-ALA induced PDT.