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Cited by 56Photodynamic Therapy Research StudiesNanoplatforms for cancer theranosticsPorphyrin Metabolism and Disorders

Mechanistic study of PpIX accumulation using the JFCR39 cell panel revealed a role for dynamin 2-mediated exocytosis

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Kitajima, Yuya, Ishii, Takuya, Kohda, Takeo, Ishizuka, Masahiro, Yamazaki, Kanami, Nishimura, Yumiko, Tanaka, Tohru, Dan, Shingo +1 more·2019·Scientific Reports
DOI 10.1038/s41598-019-44981-yPMC PMC6572817
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Abstract

5-aminolevulinic acid (5-ALA) has recently been employed for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA-PDT) of various types of cancer because hyperproliferating tumor cells do not utilize oxidative phosphorylation and do not efficiently produce heme; instead, they accumulate protoporphyrin IX (PpIX), which is a precursor of heme that is activated by violet light irradiation that results in the production of red fluorescence and singlet oxygen. The efficiencies of ALA-PDD and ALA-PDT depend on the efficient cellular uptake of 5-ALA and the inefficient excretion of PpIX. We employed the JFCR39 cell panel to determine whether tumor cells originating from different tissues can produce and accumulate PpIX. We also investigated cellular factors/molecules involved in PpIX excretion by tumor cells with the JFCR39 cell panel. Unexpectedly, the expression levels of ABCG2, which has been considered to play a major role in PpIX extracellular transport, did not show a strong correlation with PpIX excretion levels in the JFCR39 cell panel, although an ABCG2 inhibitor significantly increased intracellular PpIX accumulation in several tumor cell lines. In contrast, the expression levels of dynamin 2, which is a cell membrane-associated molecule involved in exocytosis, were correlated with the PpIX excretion levels. Moreover, inhibitors of dynamin significantly suppressed PpIX excretion and increased the intracellular levels of PpIX. This is the first report demonstrating the causal relationship between dynamin 2 expression and PpIX excretion in tumor cells.

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Authors
Kitajima, Y., Ishii, T., Kohda, T., Ishizuka, M., Yamazaki, K., Nishimura, Y., Tanaka, T., Dan, S., & Nakajima, M.
Affiliations
  • SBI Pharmaceuticals (Japan) (JP)
  • Japanese Foundation For Cancer Research (JP)
Corresponding author
  • Dan, Shingo
  • Nakajima, Motowo
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-06-17
Volume
9
Issue
1
Pages
8666-8666
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-44981-y
PMC
PMC6572817
OpenAlex
W2951540040
Cited by
56
References
67
Citations by year
2026: 6 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 12 · 2021: 4 · 2020: 16 · 2019: 1
FWCI
6.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
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
protoporphyrin IX, 5-aminolevulinic acid, photodynamic diagnosis, photodynamic therapy, dynamin 2, exocytosis, ABCG2, cancer cell lines, ABCG2 inhibitors, heme biosynthesis
MeSH terms
Aminolevulinic Acid, Exocytosis, Heme, Humans, Microscopy, Fluorescence, Mitochondria, Photochemotherapy, Protoporphyrins, Ultraviolet Rays, Photosensitizing Agents, Dynamin II, Cell Line, Tumor, Trimethyl Ammonium Compounds

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