Verification of 5-aminolevurinic radiodynamic therapy using a murine melanoma brain metastasis model

Junko Takahashi, Shinsuke Nagasawa, Mitsushi J. Ikemoto, Chikara Sato, Mari Sato, Hitoshi Iwahashi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Melanoma is a highly aggressive cancer with a propensity for brain metastases. These can be treated by radiotherapy, but the radiation-resistant nature of melanoma makes the prognosis for melanoma patients with brain metastases poor. Previously, we demonstrated that treatment of mice with subcutaneous melanoma with 5-aminolevurinic acid (5-ALA) and X-rays in combination, (“radiodynamic therapy (RDT)”), instead of with 5-ALA and laser beams (“photodynamic therapy”), improved tumor suppression in vivo. Here, using the B16-Luc melanoma brain metastasis model, we demonstrate that 5-ALA RDT effectively treats brain metastasis. We also studied how 5-ALA RDT damages cells in vitro using a B16 melanoma culture. Cell culture preincubated with 5-ALA alone increased intracellular photosensitizer protoporphyrin IX. On X-ray irradiation, the cells enhanced their ·OH radical generation, which subsequently induced γH2AX, a marker of DNA double-strand breaks in their nuclei, but decreased mitochondrial membrane potential. After two days, the cell cycle was arrested. When 5-ALA RDT was applied to the brain melanoma metastasis model in vivo, suppression of tumor growth was indicated. Therapeutic efficacy in melanoma treatment has recently been improved by molecular targeted drugs and immune checkpoint inhibitors. Treatment with these drugs is now expected to be combined with 5-ALA RDT to further improve therapeutic efficacy.

Original languageEnglish
Article number5155
JournalInternational journal of molecular sciences
Volume20
Issue number20
DOIs
Publication statusPublished - 2019 Oct 2
Externally publishedYes

Keywords

  • 5-aminolevurinic acid
  • Brain metastases
  • DNA double-strand break
  • Melanoma
  • Photodynamic therapy
  • Protoporphyrin IX
  • Radiodynamic therapy
  • Radiotherapy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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