Suramin sensitizes cells to ionizing radiation by inactivating DNA-dependent protein kinase

Yoshio Hosoi, Yoshihisa Matsumoto, Atsushi Enomoto, Akinori Morita, Joseph Green, Keiichi Nakagawa, Kiyoshi Naruse, Norio Suzuki

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Here we report that suramin sensitizes LM217, MDA-MB-468, T98G and A431 cells to ionizing radiation. Suramin sensitized cells to X radiation in a dose-dependent fashion, and longer exposure to suramin before X irradiation resulted in more efficient sensitization. The dose-modifying factors calculated from the survival curves were 1.18 in LM217 cells and 1.37 in MDA-MB-468 cells. Suramin did not sensitize Scid cells that had no DNA-dependent protein kinase activity. Suramin inhibited DNA-dependent protein kinase activity in vitro and in vivo. The concentration of suramin resulting in 50% inhibition in vitro was 1.7 μM in LM217 cells and 2.4 μM in MDA-MB-468 cells. Exposure of LM217 and MDA-MB-468 cells to suramin did not affect the level of Ku70 (G22P1) or Ku80 (XRCC5), but it increased the level of DNA-PKcs (PRKDC). Suramin did not sensitize LM217 or MDA-MB-468 cells to UV radiation. Suramin's effects were not caused by accumulation of cells in a specific phase of the cell cycle. These results suggest that suramin sensitizes cells to ionizing radiation by inhibiting DNA-dependent protein kinase activity.

Original languageEnglish
Pages (from-to)308-314
Number of pages7
JournalRadiation Research
Volume162
Issue number3
DOIs
Publication statusPublished - 2004 Sep

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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