Title: Phenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cells
Authors : Hefti, Martin
Albert, Ina
Luginbühl, Vera
Published in : Journal of Neuro-Oncology
Volume(Issue) : 108
Issue : 3
Pages : 443
Pages to: 450
Publisher / Ed. Institution : Springer
Issue Date: 2012
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (publication)
Language : German
Subjects : Fluorescence-guided surgery; Photodynamic therapy; Glioblastoma multiforme; 5-Aminolevulinic acid; Brain Tumor
Subject (DDC) : 615: Pharmacology and therapeutics
616: Internal medicine and diseases
Abstract: Epileptic seizures are among the presenting clinical signs of malignant glioma patients, frequently necessitating treatment with antiepileptic drugs (AEDs). The efficacy of 5-aminolevulinic acid (5-ALA)-based intraoperative fluorescence-guided surgery and photodynamic therapy (PDT) in glioblastoma multiforme (GBM) patients depends on the specific accumulation and total amount of intracellularly synthesized protoporphyrin IX (PpIX) in tumour cells. In this study, we investigated the effect of the AEDs phenytoin (PHY) and levetiracetam (LEVE) on 5-ALA-induced PpIX accumulation in two glioma cell lines (U373 MG and U-87 MG) and primary GBM cells isolated from a human biopsy. After treatment with PHY and LEVE for three days cells were incubated with 1 mM 5-ALA for 4 h and PpIX accumulation was determined by fluorescence measurement. We observed a decrease in PpIX synthesis of up to 55 ± 12 % in primary GBM cells after incubation with phenytoin. This reduction was dose-dependent for all tested cell lines and primary GBM cells. LEVE on the other hand did not alter PpIX concentration in GBM cells. PDT was performed in vitro by irradiating the GBM cells with light doses from 0.5 to 10 J cm-2 at 627 nm after AED and 5-ALA treatment. Although less PpIX accumulated in PHY-treated cells, efficacy of PDT was not affected. We assume that damage to the mitochondrial membrane by PHY inhibits PpIX synthesis in vitro, because we showed mitochondrial dysfunction as a result of reduced mitochondrial membrane potential in PHY-treated cells. No change in glutathione status was observed. To evaluate further the effect of PHY on PpIX fluorescence, and to establish its significance in clinical practice, animal and clinical studies are required, because the results presented here imply PHY may reduce intracellular accumulation of PpIX in patients with highgrade gliomas.
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Article in scientific journal
DOI : 10.1007/s11060-012-0857-9
ISSN: 0167-594X
1573-7373
URI: https://digitalcollection.zhaw.ch/handle/11475/12923
Appears in Collections:Publikationen Life Sciences und Facility Management

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