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Cited by 17Photodynamic Therapy Research StudiesNanoplatforms for cancer theranosticsPorphyrin Metabolism and Disorders

Iron chelation promotes 5-aminolaevulinic acid-based photodynamic therapy against oral tongue squamous cell carcinoma

Qin, Jiaqi, Zhou, Ce, Zhu, Mengqi, Shi, Shurui, Zhang, Lianyun, Zhao, Yanhong, Li, Changyi, Wang, Yinsong +1 more·2020·Photodiagnosis and Photodynamic Therapy
DOI 10.1016/j.pdpdt.2020.101907
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Abstract

Background Oral tongue squamous cell carcinoma (OTSCC) is the most common malignancy of the oral cavity. Photodynamic therapy (PDT) has become a clinically promising approach for early stage OTSCC treatment. 5-Aminolaevulinic acid (5-ALA) is a precursor of protoporphyrin IX (PpIX) and has been applied for PDT of cancer. However, the accumulated PpIX in 5-ALA-treated cancer cells will be further transformed into heme through ferrous iron insertion under ferrochelatase catalysis. Theoretically, iron chelation can enhance the intracellular accumulation of PpIX and thus promote 5-ALA-based PDT. Here, an iron chelator deferasirox (DFX) was used to investigate synergistic suppression effects of 5-ALA-based PDT and iron chelation on OTSCC. Methods In OTSCC SCC-25 cells, the enhancing effect of DFX on 5-ALA-mediated accumulation of PpIX was firstly assessed. After laser irradiation (635 nm, 200 mW/cm 2 and 2 min), the synergistic cytotoxicity and apoptosis-inducing effect of 5-ALA and DFX were evaluated in SCC-25 cells, and the apoptosis mechanism was further investigated by monitoring the change of mitochondrial membrane potential and observing the subcellular localization of cytochrome c (Cyt c). In SCC-25 tumor-bearing mice, the synergistic suppression effects of 5-ALA-based PDT and DFX on tumor growth and tumor angiogenesis were investigated after laser irradiation on the tumor (635 nm, 150 mW/cm 2 and 10 min). Results In SCC-25 cells, DFX showed strong iron chelation effect and enhanced 5-ALA-mediated intracellular accumulation of PpIX by 2-3 folds. After laser irradiation (635 nm, 200 mW/cm 2 and 2 min), 5-ALA combined with DFX exhibited significant synergistic effects on cytotoxicity and cell apoptosis. In the treated cells, the damage of mitochondrial membrane and the release of Cyt c from mitochondria to cytoplasm were observed distinctly, indicating the activation of mitochondria-related signal pathway. In SCC-25 tumor-bearing mice, tumor growth and tumor angiogenesis were both notably suppressed by combination treatment of 5-ALA with laser irradiation and DFX. Meanwhile, no obvious toxic injuries were visible in histological examination of major organs in the treated mice. Conclusions 5-ALA-based PDT combined with iron chelation synergistically inhibited the growth of OTSCC. Hence it can be seen that this combination therapy may represent a promising strategy for clinical treatment of OTSCC and other cancers.

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  • DFX has shown strong enhancement of ALA-PpIX and PDT in both SCC-25 human squamous cell carcinoma cell line and mouse tumor model.

    “In addition to DFO, another FDA-approved iron chelator deferasirox (DFX) has also shown strong enhancement of ALA-PpIX and PDT in both SCC-25 human squamous cell carcinoma cell line and mouse tumor model [91].”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [91]

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Authors
Qin, J., Zhou, C., Zhu, M., Shi, S., Zhang, L., Zhao, Y., Li, C., Wang, Y., & Wang, Y.
Affiliations
Tianjin Medical University (CN)
Corresponding author
  • Wang, Yinsong
  • Wang, Yue
ORCID
Venue
Photodiagnosis and Photodynamic Therapy
Publisher
Elsevier BV
Published
2020-09
Volume
31
Pages
101907
ISSN
1572-1000 (ISSN-L)
DOI
10.1016/j.pdpdt.2020.101907
OpenAlex
W3040397718
Cited by
17
References
43
Citations by year
2026: 2 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 1 · 2021: 1
FWCI
0.70
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Photodiagnosis and Photodynamic Therapy (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
Keywords
oral tongue squamous cell carcinoma, photodynamic therapy, 5-aminolevulinic acid, iron chelation, deferasirox, protoporphyrin IX, ferrochelatase, ferrous iron, apoptosis, mitochondrial membrane potential, cytochrome c release, tumor angiogenesis, combination therapy, synergistic cytotoxicity, tumor growth inhibition
MeSH terms
Squamous Cell Carcinoma of Head and Neck, Aminolevulinic Acid, Animals, Carcinoma, Squamous Cell, Head and Neck Neoplasms, Iron Chelating Agents, Photochemotherapy, Protoporphyrins, Tongue Neoplasms, Photosensitizing Agents, Mice

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