Dna strand break properties of protoporphyrin ix by x-ray irradiation against melanoma

Takema Hasegawa, Junko Takahashi*, Shinsuke Nagasawa, Motomichi Doi, Akihiro Moriyama, Hitoshi Iwahashi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Recent reports have suggested that 5-aminolevulinic acid (5-ALA), which is a precursor to protoporphyrin IX (PpIX), leads to selective accumulation of PpIX in tumor cells and acts as a radiation sensitizer in vitro and in vivo in mouse models of melanoma, glioma, and colon cancer. In this study, we investigated the effect of PpIX under X-ray irradiation through ROS generation and DNA damage. ROS generation by the interaction between PpIX and X-ray was evaluated by two kinds of probes, 3’-(p-aminophenyl) fluorescein (APF) for hydroxyl radical (•OH) detection and dihydroethidium (DHE) for superoxide (O2 •- ). •OH showed an increase, regardless of the dissolved oxygen. Meanwhile, the increase in O2 •- was proportional to the dissolved oxygen. Strand breaks (SBs) of DNA molecule were evaluated by gel electrophoresis, and the enhancement of SBs was observed by PpIX treatment. We also studied the effect of PpIX for DNA damage in cells by X-ray irradiation using a B16 melanoma culture. X-ray irradiation induced γH2AX, DNA double-strand breaks (DSBs) in the context of chromatin, and affected cell survival. Since PpIX can enhance ROS generation even in a hypoxic state and induce DNA damage, combined radiotherapy treatment with 5-ALA is expected to improve therapeutic efficacy for radioresistant tumors.

Original languageEnglish
Article number2302
JournalInternational journal of molecular sciences
Volume21
Issue number7
DOIs
Publication statusPublished - 2020 Apr 1
Externally publishedYes

Keywords

  • DNA double-strand break
  • Melanoma
  • Photodynamic therapy
  • Protoporphyrin IX
  • Radiodynamic therapy
  • Radiotherapy
  • Reactive oxygen species (ROS)
  • X-ray

ASJC Scopus subject areas

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

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