The Hydroxypyridinone Iron Chelator CP94 Can Enhance PpIX‐induced PDT of Cultured Human Glioma Cells
Abstract
Photodynamic therapy (PDT) with the pro-drugs 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) utilizes the combined interaction of a photosensitizer, light and molecular oxygen to ablate tumor tissue. To potentially increase accumulation of the photosensitizer, protoporphyrin IX (PpIX), within tumor cells an iron chelator can be employed. This study analyzed the effects of ALA/MAL-induced PDT combined with the iron chelator 1, 2-diethyl-3-hydroxypyridin-4-one hydrochloride (CP94) on the accumulation of PpIX in human glioma cells in vitro. Cells were incubated for 0, 3 and 6h with various concentrations of ALA/MAL with or without CP94 and the resulting accumulations of PpIX, which naturally fluoresces, were quantified prior to and following light irradiation. In addition, counts of viable cells were recorded. The use of CP94 in combination with ALA/MAL produced significant enhancements of PpIX fluorescence in human glioma cells. At the highest concentrations of each prodrug, CP94 enhanced PpIX fluorescence significantly at 3h for ALA and by more than 50% at 6h for MAL. Cells subsequently treated with ALA/MAL-induced PDT in combination with CP94 produced the greatest cytotoxicity. It is therefore concluded that with further study CP94 may be a useful adjuvant to photodiagnosis and/or PpIX-induced PDT treatment of glioma.
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Enhancement of PDT effects has been observed after removal of iron with iron-chelating substances such as desferrioxamine or CP94.
“Enhancement of PDT effects has been also observed after removal of iron with different iron-chelating substances such as desferrioxamine [51] or CP94 [52].”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [52]
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Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer
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- Authors
- Blake, E., & Curnow, A.
- Affiliations
- University of Exeter (GB)
- Corresponding author
- Blake, Emma
- ORCID
- Curnow, Alison
- Venue
- Photochemistry and Photobiology
- Publisher
- Wiley
- Published
- 2010-09
- Volume
- 86
- Issue
- 5
- Pages
- 1154-1160
- ISSN
- 0031-8655 (ISSN-L)
- 1751-1097
- OpenAlex
- W2079328076
- Cited by
- 51
- References
- 5
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 3 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Photochemistry and Photobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Galderma
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- photodynamic therapy, protoporphyrin IX, iron chelators, 5-aminolevulinic acid, methyl aminolevulinate, glioma cells, photosensitizer accumulation, cytotoxicity, adjuvant therapy, photodynamic diagnosis
- MeSH terms
- Cell Survival, Cells, Cultured, Glioma, Humans, Iron Chelating Agents, Photochemotherapy, Protoporphyrins, Pyridones
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