Human glioblastoma stem-like cells accumulate protoporphyrin IX when subjected to exogenous 5-aminolaevulinic acid, rendering them sensitive to photodynamic treatment

Adrian Schimanski, Lara Ebbert, Michael C. Sabel, Gaetano Finocchiaro, Katrin Lamszus, Christian Ewelt, Nima Etminan, Johannes C. Fischer, Rüdiger V. Sorg

Research output: Contribution to journalArticle

Abstract

Glioblastoma (GBM) is the most frequent and lethal primary brain tumor in adults. Despite multimodal therapy combining resection, radio- and alkylating chemotherapy, disease recurrence is universal and prognosis of patients is poor. Glioblastoma stem-like cells (GSC), which can be grown as neurospheres from primary tumors in vitro, appear to be resistant to the established therapies and are suspected to be the driving force for disease recurrence. Thus, efficacy of emerging therapies may depend on targeting GSC. 5-aminolaevulinic acid-mediated photodynamic therapy (5-ALA/PDT) is a promising therapeutic approach in GBM. It utilizes the selective accumulation of the photosensitizer protoporphyrin IX (PPIX) in GBM cells after application of 5-ALA. When exposed to laser light of 635 nm wavelength, PPIX initiates a photochemical reaction resulting in the generation of reactive oxygen species, which kill the tumor cells. Whether GSC accumulate PPIX and are sensitive to 5-ALA/PDT is currently unknown. Therefore, human GSC were derived from primary tumors and grown as neurospheres under serum free conditions. When subjected to exogenous 5-ALA, a dose- and time-dependent accumulation of PPIX in GSC was observed by flow cytometry, which varied between individual GSC preparations. Subsequent exposure to laser light of 635 nm wavelength substantially killed GSC, whereas treatment with 5-ALA or exposure to laser light only had no effect. LD50 values differed between GSC preparations, but were negatively correlated with PPIX accumulation in GSC. In summary, we report for the first time that glioblastoma stem-like cells accumulate PPIX when subjected to 5-aminolaevulinic acid and are sensitive to 5-aminolaevulinc acid based photodynamic therapy.

Original languageEnglish
Pages (from-to)203-210
Number of pages8
JournalJournal of Photochemistry and Photobiology B: Biology
Volume163
DOIs
Publication statusPublished - Oct 1 2016

Keywords

  • 5-aminolaevulinic acid
  • Cancer stem cells
  • Glioblastoma
  • Glioblastoma stem-like cells
  • Photodynamic therapy
  • Protoporphyrin IX

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Human glioblastoma stem-like cells accumulate protoporphyrin IX when subjected to exogenous 5-aminolaevulinic acid, rendering them sensitive to photodynamic treatment'. Together they form a unique fingerprint.

Cite this