YC-1 sensitizes the antitumor effects of boron neutron capture therapy in hypoxic tumor cells

Takaomi Harada, Katsumi Hirose, Yuki Wada, Mariko Sato, Koji Ichise, Masahiko Aoki, Takahiro Kato, Ken Takeda, Yoshihiro Takai

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The uptake of boron into tumor cells is a key factor in the biological effects of boron neutron capture therapy (BNCT). The uptake of boron agents is suppressed in hypoxic conditions, but themechanism of hypoxia-inducedmodulation of suppression of boron uptake is not clear. Therefore, we evaluated whether hypoxia-inducible factor 1α (HIF-1α) contributes to attenuation of the antitumor effects of BNCT in hypoxic tumor cells.We also tested whether YC-1, a HIF-1α-targeting inhibitor, has therapeutic potential with BNCT. To elucidate the mechanism of attenuation of the effects of BNCT caused by hypoxia, deferoxamine (DFO) was used in experiments. Cells were incubated in normal oxygen, hypoxic conditions (1% O2) or 5 μM DFO for 24 h. Then, cells were treated with 10B-boronophenylalanine (BPA) for 2 h and boron accumulation in cells was evaluated. To clarify the relationship between HIF-1α and Ltype amino acid transporter 1 (LAT1), gene expression was evaluated by a usingHIF-1α gene knockdown technique. Finally, to improve attenuation of the effects ofBNCTin hypoxic cells,BNCTwas combinedwithYC-1. Boron uptake was continuously suppressed up to 2 h after administration of BPA by 5 μM DFO treatment. In cells treated with 5 μMDFO, LAT1 expression was restored inHIF-1α-knocked down samples in all cell lines, revealing that HIF-1α suppresses LAT1 expression in hypoxic cells. From the results of the surviving fraction after BNCT combined with YC-1, treatment with YC-1 sensitized the antitumor effects of BNCT in cells cultured in hypoxia.

Original languageEnglish
Pages (from-to)524-534
Number of pages11
JournalJournal of radiation research
Volume61
Issue number4
DOIs
Publication statusPublished - 2020 Jul 1

Keywords

  • Boron neutron capture therapy
  • Deferoxamine
  • Hypoxia
  • Hypoxia-inducible factor 1α
  • YC-1

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

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