Ferrochelatase Deficiency Abrogated the Enhancement of Aminolevulinic Acid‐mediated Protoporphyrin IX by Iron Chelator Deferoxamine
Open accessAbstract
Aminolevulinic acid (ALA) is a prodrug that is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (Pp IX) for tumor fluorescence detection and photodynamic therapy (PDT). The iron chelator deferoxamine (DFO) has been widely used to enhance Pp IX accumulation by inhibiting the iron‐dependent bioconversion of Pp IX to heme, a reaction catalyzed by ferrochelatase (FECH). Tumor response to DFO treatment is known to be highly variable, and some tumors even show no response. Given the fact that tumors often exhibit reduced FECH expression/enzymatic activity, we examined how reducing FECH level affected the DFO enhancement effect. Our results showed that reducing FECH level by silencing FECH in SkBr3 breast cancer cells completely abrogated the enhancement effect of DFO. Although DFO enhanced ALA‐Pp IX fluorescence and PDT response in SkBr3 vector control cells, it caused a similar increase in MCF 10A breast epithelial cells, resulting in no net gain in the selectivity toward tumor cells. We also found that DFO treatment induced less increase in ALA‐Pp IX fluorescence in tumor cells with lower FECH activity (MDA‐MB‐231, Hs 578T) than in tumor cells with higher FECH activity (MDA‐MB‐453). Our study demonstrates that FECH activity is an important determinant of tumor response to DFO treatment.
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DFO increases ALA-PpIX fluorescence more after 1 h than after 4 h treatment and there is an inverse correlation between PpIX fluorescence and the enhancement effect of DFO.
“Particularly, DFO increases ALA-PpIX fluorescence more after 1 h than after 4 h treatment and there is an inverse correlation between PpIX fluorescence and the enhancement effect of DFO.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [106]
The Results report that DFO increased ALA-PpIX fluorescence in control cells but not in FECH-knockdown cells, which had higher PpIX fluorescence (sections on DFO treatment and FECH knockdown; page unavailable). This is consistent with the claimed inverse relationship in those cell lines, but the paper does not establish a general inverse correlation. The Flow cytometry Methods describe a 4-hour treatment, not a comparison showing greater enhancement after 1 hour. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOur results indicate that the effects of DFO are dependent on the duration of treatment and FECH expression.
“Furthermore, our results indicate that the effects of DFO are dependent on the duration of treatment and FECH expression [106,107].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [106]
The Results and Discussion report that FECH knockdown abolished DFO’s enhancement of ALA-PpIX fluorescence and that cell lines with lower FECH activity responded less. The Methods describe a 4-hour drug incubation, but the paper does not compare treatment durations or establish that DFO’s effects depend on duration. (LLM, conf=0.88)
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- Authors
- Palasuberniam, P., Kraus, D., Mansi, M., Braun, A., Howley, R., Myers, K. A., & Chen, B.
- Affiliations
- University of the Sciences (US)
- Corresponding author
- Chen, Bin
- Venue
- Photochemistry and Photobiology
- Publisher
- Wiley
- Published
- 2019-03-15
- Volume
- 95
- Issue
- 4
- Pages
- 1052-1059
- ISSN
- 0031-8655 (ISSN-L)
- 1751-1097
- PMC
- PMC6642023
- OpenAlex
- W2914538391
- Cited by
- 23
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 1
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Photochemistry and Photobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- National Institutes of Health (R15EB026208)
- 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
- ferrochelatase, deferoxamine, 5-aminolevulinic acid, protoporphyrin IX, heme biosynthesis, photodynamic therapy, iron chelation, breast cancer, SK-BR-3 cells, tumor selectivity
- MeSH terms
- Aminolevulinic Acid, Breast Neoplasms, Deferoxamine, Epithelial Cells, Female, Ferrochelatase, Humans, Photochemotherapy, Protoporphyrins, Siderophores, Photosensitizing Agents, Gene Silencing, Cell Line, Tumor
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