Suramin sensitizing cells to ionizing radiation by inactivating DNA-dependent protein kinase.
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.
Hosoi
Yoshio
Y
Department of Radiation Oncology, Faculty of Medicine, University of Tokyo, Japan. hosoi@m.u-tokyo.ac.jp
Matsumoto
Yoshihisa
Y
Enomoto
Atsushi
A
Morita
Akinori
A
Green
Joseph
J
Nakagawa
Keiichi
K
Naruse
Kiyoshi
K
Suzuki
Norio
N
D002460:Cell Line; D045744:Cell Line, Tumor / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology* / Q000532:radiotherapy; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000187:drug effects; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents; D013498:Suramin / Q000008:administration & dosage*; D014466:Ultraviolet Rays; D014965:X-Rays
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011838:Radiation-Sensitizing Agents; D013498:Suramin; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases