Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins
Open accessAbstract
Selective destruction of Friend erythroleukaemic cells (FELC) was potentiated by stimulation of endogenous porphyrin synthesis followed by light sensitization. Endogenous porphyrin biosynthesis in FELC was induced by supplementation of 5-amino levulinic acid (5-ALA) at a concentration of 5 X 10(-4) M. The main accumulated product, after 4 days culture, was uroporphyrin, while after 8 days culture the cells were loaded with protoporphyrin, up to 1.5 micrograms 10(-7) cells. Photoirradiation of the cells for 2 min, accumulating endogenous porphyrins, induced cardinal deformations and cell disintegration in greater than 95% of the cells, as examined by scanning electron microscopy (SEM). The photodynamic destruction effects were dependent on cultivation time with 5-ALA. Flow cytometry analysis showed an immediate expansion of cell volume subsequent to irradiation, presumably a consequence of water influx. Transmission electron microscopy (TEM) of photosensitized cells after different time intervals of culture in 5-ALA medium, revealed initial damage to mitochondria and water influx into the nuclear envelope, after 2 days. After 3-4 days in culture the water influx phenomenon was pronounced, chromatin condensation took place and slight rupture of the outer membrane was detected. Cells photosensitized after 5-6 days of culture were completely disintegrated leaving a nuclear remnant and an enormously swollen nuclear envelope. The culture time dependence of the process, showed an interrelationship between the photodynamic effect and porphyrin accumulation sites in cellular compartments. The study presents a specific method for erythroleukaemic cell inactivation.
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Photoactivation of endogenous PpIX induced by ALA results in elimination of erythroleukemia cells.
“Photoactivation of endogenous PpIX induced by ALA results in the elimination of erythroleukemia cells as Malik et al. showed in 1987, which is the first report of using ALA-PDT for cell inactivation [5].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [5]
The Summary (p. 589) reports that ALA-treated Friend erythroleukaemia cells accumulated protoporphyrin and that irradiation disintegrated more than 95% of cells. The Discussion also reports photoinactivation, but says both uroporphyrin and protoporphyrin may act as photosensitizers; our copy does not establish the citing sentence’s additional claim that this was the first report of ALA-PDT for cell inactivation. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn 1987 ALA was used for the first time in photodynamic therapy as a porphyrin precursor for selective elimination of erythroleukaemic cells.
“In 1987 ALA was used for the first time in photodynamic therapy as a porphyrin precursor for selective elimination of erythroleukaemic cells [89].”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [89]
The Summary (p. 589) reports that 5-ALA stimulated porphyrin synthesis in Friend erythroleukaemic cells and that light exposure selectively destroyed the cells. The paper does not establish that this was the first use of ALA in photodynamic therapy; that priority claim is unsupported by our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredExogenously applied ALA induces enhanced PpIX biosynthesis in tumor cells.
“The finding that enhanced PpIX biosynthesis can be induced by exogenously applied ALA in tumor cells has led to the use of ALA as a prodrug for PpIX-mediated photodynamic therapy (PDT) and photodiagnosis [5,6].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [5]
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References 27 · Cited by 292
- Authors
- Malik, Z., & Lugaci, H.
- Affiliations
- Bar-Ilan University (IL)
- ORCID
- Malik, Z
- Venue
- British Journal of Cancer
- Published
- 1987-11
- Volume
- 56
- Issue
- 5
- Pages
- 589-595
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2001902
- OpenAlex
- W2040262244
- Cited by
- 292
- References
- 27
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 5 · 2022: 5 · 2021: 13 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 10 · 2014: 6 · 2013: 6 · 2012: 5
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- British Journal of Cancer (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Bar-Ilan University
- 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
- photodynamic therapy, erythroleukemia, endogenous porphyrins, 5-aminolevulinic acid, porphyrin synthesis, uroporphyrin, protoporphyrin IX, photosensitization, cell disintegration, mitochondrial damage, chromatin condensation
- MeSH terms
- Aminolevulinic Acid, Animals, Cell Survival, Coproporphyrins, Leukemia, Erythroblastic, Acute, Friend murine leukemia virus, Levulinic Acids, Microscopy, Electron, Photochemotherapy, Porphyrins, Protoporphyrins, Time Factors, Tumor Cells, Cultured, Uroporphyrinogens
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