ArticleNeuro-oncology advances
Combination chemotherapy potentiates 5-aminolevulic acid-mediated photodynamic therapy killing of patient-derived glioma stem-like cells
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) is a promising therapy for glioblastoma (GBM). 5-ALA induces tumor-selective accumulation of protoporphyrin IX (PPIX). Photoactivation of PPIX induces reactive oxygen species generation and tumor cell death. Glioma stem-like cells (GSC) are hypothesized to be resistant to standard therapies and contribute to GBM recurrence. Differential PPIX accumulation in GSC could lead to treatment resistance. We investigated if chemotherapeutics currently utilized in GBM treatment, temozolomide (TMZ) and bis-chloroethylnitrosurea (BCNU), could potentiate 5-ALA PDT killing of GSC. Methods: Patient-derived GSC lines were established. PPIX accumulation was assessed with flow cytometry. 5-ALA metabolic enzyme mRNA expression was measured with quantitative real-time PCR (qRT-PCR). BCNU or TMZ was co-administered with 5-ALA prior to laser irradiation. The effect of combination therapy was evaluated using Loewe combination index analysis. Results: Three GSC lines were exposed to 5-ALA Conclusions: We report the effect of combination chemotherapy and 5-ALA PDT on GSC viability, demonstrating the potential for BCNU and 5-ALA PDT to work synergistically. We speculate that HMOX1 upregulation by BCNU could mitigate this effect.
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