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

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 microM in LM217 cells and 2.4 microM 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.

journal_name

Radiat Res

journal_title

Radiation research

authors

Hosoi Y,Matsumoto Y,Enomoto A,Morita A,Green J,Nakagawa K,Naruse K,Suzuki N

doi

10.1667/rr3217

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

308-14

issue

3

eissn

0033-7587

issn

1938-5404

journal_volume

162

pub_type

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