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Cited by 8Photodynamic Therapy Research StudiesPorphyrin Metabolism and DisordersNanoplatforms for cancer theranostics

Analysis of Renal Cell Carcinoma Cell Response to the Enhancement of 5‐aminolevulinic Acid‐mediated Protoporphyrin IX Fluorescence by Iron Chelator Deferoxamine†

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Howley, Richard, Mansi, Matthew, Shinde, Janhavi, Restrepo, Juliana, Chen, Bin·2023·Photochemistry and Photobiology
DOI 10.1111/php.13678PMC PMC10258817
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Abstract

As a tumor photodiagnostic agent, 5‐aminolevulinic acid (ALA) is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (PpIX) with fluorescence. ALA‐PpIX fluorescence was evaluated in human renal cell carcinoma (RCC) cell lines and non‐tumor HK‐2 cell lines. We found that extracellular PpIX level was correlated with ABCG2 activity, illustrating its importance as a PpIX efflux transporter. Extracellular PpIX was also related to the Km of ferrochelatase (FECH) that chelates PpIX with ferrous iron to form heme. The Vmax of FECH was higher in all RCC cell lines tested than in the HK‐2 cell line. TCGA dataset analysis indicates a positive correlation between FECH expression and RCC patient survival. These findings suggest FECH as an important biomarker in RCC. Effects of iron chelator deferoxamine (DFO) on the enhancement of PpIX fluorescence were assessed. DFO increased intracellular PpIX in both tumor and non‐tumor cells, resulting in no gain in tumor/non‐tumor fluorescence ratios. DFO appeared to increase ALA‐PpIX more at 1‐h than at 4‐h treatment. There was an inverse correlation between ALA‐PpIX fluorescence and the enhancement effect of DFO. These results suggest that enhancement of ALA‐PpIX by DFO may be limited by the availability of ferrous iron in mitochondria following ALA administration.

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  • Our 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 [107]

    The Results and Discussion report greater DFO-induced PpIX fluorescence enhancement after 1 hour than after 4 hours, supporting a treatment-duration effect. The Discussion says the DFO-induced change was not correlated with either measured FECH activity parameter (Vmax or Km); it does not establish dependence on FECH expression. Page numbers were not provided in our copy. (LLM, conf=0.88)

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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 [107]

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Cited by

Sorted by citations

Authors
Howley, R., Mansi, M., Shinde, J., Restrepo, J., & Chen, B.
Affiliations
Saint Joseph's University (US)
Corresponding author
Chen, Bin
ORCID
Venue
Photochemistry and Photobiology
Publisher
Wiley
Published
2022-08
Volume
99
Issue
2
Pages
787-792
ISSN
  • 0031-8655 (ISSN-L)
  • 1751-1097
DOI
10.1111/php.13678
PMC
PMC10258817
OpenAlex
W4286007745
Cited by
8
References
4
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 1
FWCI
1.13
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Photochemistry and Photobiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R15CA268200)
  • National Institute of Biomedical Imaging and Bioengineering (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 › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Keywords
renal cell carcinoma, 5-aminolevulinic acid, protoporphyrin IX, deferoxamine, iron chelation, ferrochelatase, ABCG2, heme biosynthesis, tumor markers, HK-2 cells
MeSH terms
Aminolevulinic Acid, Carcinoma, Renal Cell, Deferoxamine, Fluorescence, Heme, Humans, Iron, Iron Chelating Agents, Kidney Neoplasms, Photochemotherapy, Protoporphyrins, Photosensitizing Agents, Cell Line, Tumor

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