Photodynamic therapy with 5-aminolevulinic acid: A new diagnostic, therapeutic, and surgical aid for neuroblastoma

Toshihiko Watanabe, Yoshiaki Nishio, Yuki Yamamoto, Takahiro Shimizu, Xiao Kang Li, Hajime Okita, Tatsuo Kuroda

研究成果: Article査読

2 被引用数 (Scopus)


Background: 5-Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) is widely used in cancer therapy because of the tumor-specific accumulation of photosensitizing protoporphyrin IX (PpIX). We aimed to assess the susceptibility of human neuroblastoma cell lines to ALA-PDT and determine the mechanism of PDT. Methods: We used four human neuroblastoma cell lines (GOTO, NB9, IMR32, and NB1) and a gastric cancer cell line (MKN45) as a positive control. Cells were treated with increasing concentrations of ALA, and the ALA-induced production of PpIX in tumor cells was quantified using fluorescence spectrophotometry. PDT photocytotoxicity was measured by exposing the cells to a 630-nm irradiation for 10 min, and apoptotic cells stained with phosphatidylserine (PS) and propidium iodide (PI) were detected through flow cytometry. Results: ALA cytotoxicity was not observed in any cell line. The intracellular concentration of PpIX increased in an ALA dose-dependent manner, and intracellular fluorescence of PpIX increased in a time-dependent manner. The viability of NB-1 cells treated with 250 μM 5-ALA rapidly decreased to 5%. Photocytotoxicity was observed in the following order: NB1, IMR32, NB-9, and GOTO. Photocytotoxicity was positively correlated with intracellular PpIX concentrations. PS+/PI- cells increased up to 21% after 12 h, and PS+/PI+ cells accounted for 35% of all cells after 24 h, which suggests that ALA-PDT induced apoptotic cell death. Conclusion: This study shows that neuroblastoma cell lines were susceptible to 5-ALA-PDT, resulting in persistent apoptotic cell death. Levels of evidence: N/A for basic study.

ジャーナルJournal of Pediatric Surgery
出版ステータスPublished - 2022 7月

ASJC Scopus subject areas

  • 外科
  • 小児科学、周産期医学および子どもの健康


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