The influence of hypoxia and pH on aminolaevulinic acid-induced photodynamic therapy in bladder cancer cells in vitro
Open accessAbstract
Photodynamic therapy (PDT) is a cancer treatment based on the interaction of light and a photosensitizing chemical. The photosensitizer protoporphyrin IX (PpIX) is generated via the haem biosynthetic pathway after administration of aminolaevulinic acid (ALA). The cellular microenvironment of tumours is hypoxic and acidotic relative to normal tissue, which may influence PpIX generation and compromise PDT efficacy. This study used bladder cancer cells, incubated with ALA at various oxygen tensions and H+ ion concentrations, and assessed the effects on PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2.5% (19 mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mmHg) oxygen (0.15, 0.28 and 0.398 ng microg(-1) protein compared with 0.68 ng microg(-1) respectively; P < 0.05). The response to PDT was abolished by hypoxia, as a result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng microg(-1)) compared with that at pH 7.4 and 5.5 (0.41 and 0.55 ng microg(-1) respectively). PDT cytotoxicity was enhanced at lower pH values. These results suggest that ALA-induced PDT may be inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may slightly enhance the efficacy of ALA-induced PDT.
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Other parameters that affect PpIX accumulation include pH, oxygen availability, illumination conditions, or thickness of stratum corneum.
“Other parameters that affect PpIX accumulation include pH [63,64,65], oxygen availability [63,66], illumination conditions, or thickness of striatum corneum [67].”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [63]
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- Authors
- Wyld, L., Reed, M., & Brown, N.
- Affiliations
- Royal Hallamshire Hospital (GB)
- ORCID
- Wyld, L
- Venue
- British Journal of Cancer
- Published
- 1998-05
- Volume
- 77
- Issue
- 10
- Pages
- 1621-1627
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2150064
- OpenAlex
- W2030168336
- Cited by
- 82
- References
- 32
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 10 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- British Journal of Cancer (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- 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, aminolaevulinic acid, protoporphyrin IX, hypoxia, tumor acidosis, bladder cancer cells, photosensitizer synthesis, heme biosynthesis, oxygen partial pressure, pH
- MeSH terms
- Acidosis, Aminolevulinic Acid, Urinary Bladder Neoplasms, Cell Survival, Humans, Hydrogen-Ion Concentration, Photochemotherapy, Protoporphyrins, Tumor Cells, Cultured, Cell Hypoxia, Photosensitizing Agents
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