Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo
Open accessAbstract
The ability of 5-aminolaevulinic acid and some of its esterified derivatives to induce porphyrin accumulation has been examined in CaNT murine mammary carcinoma cells growing in culture and as tumours in vivo. Topical or intravenous administration of 5-aminolaevulinic acid-esters to mice bearing subcutaneous tumours produced lower porphyrin levels in the tumour than an equimolar dose of 5-aminolaevulinic acid. Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation. A number of normal tissues accumulated higher concentrations of porphyrins than tumour tissue following intravenous administration of 5-aminolaevulinic acid-esters. Esterase activity in these normal tissues was greater than that in tumour tissue. In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length. Tumour cells growing in culture released esterase activity into the medium. These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs.
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The advantage of ALA esters in comparison to ALA-induced PpIX formation is not a general rule; some researchers report that it depends on esterase activity which varies within tissues or cell lines used in studies.
“The advantage of ALA esters in comparison to ALA-inducedPpIX formation is not a general rule, some researchers report that it depends on esterase activity which varies within the tissues or cell lines used in the studies [73,74].”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [73]
The Results section ('Esterase activity in murine tissues and cultured cells') reports that esterase activity varied among tissues and that higher activity generally accompanied greater porphyrin accumulation after ALA-ester administration. The Discussion also finds that esters were less effective than ALA in tumours in vivo despite performing similarly or better in cultured cells. It offers esterase activity as a possible explanation, however, rather than establishing that the advantage depends on esterase activity across tissues or cell lines. (LLM, conf=0.84)
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References 30 · Cited by 37
Research works printed but not linked: 24
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- Authors
- Tunstall, R. G., Barnett, A. A., Schofield, J., Griffiths, J., Vernon, D. I., Brown, S. B., & Roberts, D. J. H.
- Affiliations
- University of Leeds (GB)
- Corresponding author
- Roberts, D J H
- Venue
- British Journal of Cancer
- Published
- 2002-07
- Volume
- 87
- Issue
- 2
- Pages
- 246-250
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2376104
- OpenAlex
- W2006601851
- Cited by
- 37
- References
- 30
- Citations by year
- 2026: 1 · 2022: 1 · 2019: 2 · 2015: 2 · 2014: 1 · 2012: 1
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Engineering and Physical Sciences Research Council
- 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 › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
- Keywords
- porphyrin accumulation, photodynamic therapy, prodrugs, esterase activity, cancer cells, topical administration, intravenous administration, dose dependence, ester chain length
- MeSH terms
- Administration, Cutaneous, Aminolevulinic Acid, Animals, Antineoplastic Agents, Carboxylic Ester Hydrolases, Carcinoma, Chromatography, High Pressure Liquid, Dose-Response Relationship, Drug, Esters, Female, Injections, Intravenous, Mammary Neoplasms, Experimental, Mice, Inbred CBA, Neoplasm Proteins, Photochemotherapy, Porphyrins, Prodrugs, Protoporphyrins, Tumor Cells, Cultured, Photosensitizing Agents, Carboxylesterase, Mice
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