Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase
Open accessAbstract
The mechanism of porphyrin accumulation by tumours is not yet established. If metabolism aids porphyrin elimination, tumours, unlike normal tissues, may not metabolize porphyrins used clinically, such as proto-, haemato-, OO'-diacetyl-haemato- and monohydroxyethyl-monovinyl-deutero-porphyrin. Proto-, haemato- and monohydroxyethyl-monovinyl-deutero-porphyrin are substrates for the mitochondrial enzyme ferrochelatase (EC 4.99.1.1), which can form haem analogues from exogenous porphyrins. The Km values for proto-, haemato- and monohydroxyethyl-monovinyl-deutero-porphyrin are 11, 22 and 23 microM respectively. However, OO'-diacetyl-haematoporphyrin is an effective competitive inhibitor with Ki of 11 microM. Hepatic ferrochelatase specific activity is 5.9 and 5.5 nmol of haem/h per mg of protein respectively in normal Buffalo rat and in those bearing the extrahepatic Morris 7288C hepatoma, and is only 0.13 nmol/h per mg in the hepatomas. Therefore low ferrochelatase activity in cancerous cells may provide one means whereby some porphyrins accumulate in tumours, and the ability of certain porphyrins to act as ferrochelatase inhibitors may provide another.
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Although the uptake of ALA is non-selective, accumulation of PpIX in tumor cells may occur selectively because of alterations in enzymatic activity in the heme synthesis pathway.
“Although the uptake of ALA is non-selective, accumulation of PpIX in tumor cells may occur selectively because of alterations in enzymatic activity in the heme synthesis pathway.”
From Photodynamic Therapy for Non-Melanoma Skin Cancers (2016) · cites this paper as [10]
The accumulation of PpIX in neoplastic tissue is further supplemented by decreased activity of ferrochelatase (FC), which converts PpIX to heme.
“The accumulation of PpIX in neoplastic tissue is further supplemented by decreased activity of ferrochelatase (FC), which converts PpIX to heme [9,10].”
From Photodynamic Therapy for Non-Melanoma Skin Cancers (2016) · cites this paper as [10]
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Combination of PDT and inhibitor treatment affects melanoma cells and spares keratinocytes
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Color auto-fluorescence from cancer lesions: Improved detection of central type lung cancer
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Efficacy of intravenous delta-aminolaevulinic acid photodynamic therapy on rabbit papillomas
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Activity of phosphatase-sensitive 5-aminolevulinic acid prodrugs in cancer cell lines
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Photosensitiser delivery for photodynamic therapy. Part 1: Topical carrier platforms
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The role of arginyl residues in porphyrin binding to ferrochelatase.
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Interstitial photodynamic therapy in a rat liver metastasis model
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Fluorescent contrast agents for tumor surgery (Review)
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Spectroscopic examination of the active site of bovine ferrochelatase
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TMC-435, an NS3/4A protease inhibitor for the treatment of HCV infection.
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[48] Purification and characterization of bacterial ferrochelatase
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Photodynamic therapy and laser-based diagnostic studies of malignant tumours
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Photodynamic Therapy Effectively Treats Actinic Keratoses Without Pre-Illumination Incubation Time.
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Unilesional mycosis fungoides treated with photodynamic therapy. A case report.
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- Authors
- Dailey, H. A., & Smith, A.
- ORCID
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1984-10-15
- Volume
- 223
- Issue
- 2
- Pages
- 441-445
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1144316
- OpenAlex
- W2170447022
- Cited by
- 140
- References
- 30
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 3 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 1 · 2012: 3
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Sedimentological Research Group
- National Institutes of Health
- U.S. Public Health Service
- 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
- porphyrins, ferrochelatase, photodynamic therapy, hematoporphyrin, deuteroporphyrin, competitive inhibition, enzyme kinetics, hepatocellular carcinoma
- MeSH terms
- Animals, Ferrochelatase, Hematoporphyrins, Kinetics, Liver, Liver Neoplasms, Experimental, Lyases, Male, Porphyrins, Rats, Inbred BUF, Rats, In Vitro Techniques
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