Research Project
Grant-in-Aid for Scientific Research (B)
Phosphorothioate oligonucleotides and suramin bind to heparin binding proteins including DNA polymerases, and inhibit their functions. In the present study, we report inhibition of DNA-dependent protein kinase (DNA-PK) activity by phosphorothioate oligonucleotides and suramin. Inhibitory effect of phosphorothioate oligonucleotides on DNA-PK activity was increased with length and reached a plateau at 36-mer. The base composition of phosphorothioate oligonucleotides did not affect the inhibitory effect. The inhibitory effect by phosphorothioate oligodeoxycytidine 36-mer can be about 200-fold greater than that by the phosphodiester oligodeoxycytidine 36-mer. The inhibitory effect was also observed with purified DNA-PK, which suggests direct interaction between DNA-PK and phosphorothioate oligonucleotides. DNA-PK will have different binding positions for double-stranded DNA and phosphorothioate oligodeoxycytidine 36-mer because they were not competitive in DNA-PK activation. Suramin sensit … More ized 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 sensitized 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 or Ku80, but it increased the level of DNA-PKcs. Suramin did not sensitize LM217 or MDA-MB-468 cells to UV radiation. Exposure to suramin inhibited the repair of DNA double-strand breaks caused by 50 Gy irradiation. 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. Less
All 2006 2005 2004 Other
All Journal Article (33 results) Book (1 results) Publications (6 results)
International Journal of Molecular Medicine (in press)
Biochemical and Biophysical Research Communications 342
Pages: 363-368
Bone Marrow Transplantation 37
Pages: 583-587
Carcinogenesis 27
Pages: 117-122
Cell Death and Differentiation 13
Pages: 499-511
World Journal of Gastroenterology 11
Pages: 7237-7241
Radiation Research 164
Pages: 723-732
Hepato-Gasteroenterology 52
Pages: 995-998
放射線生物研究 40
Pages: 360-384
Radiation Biology Research Communications 40
Institute for Environmental Sciences, Japan
Biochemical and Biophysical Research Communications 323
Pages: 816-822
Radiation Research 162
Pages: 433-441
Cancer Research 64
Pages: 6919-6923
International Journal of Oncology 25
Pages: 461-468
Pages: 308-314
癌の臨床 50
Pages: 1055-1060
日本婦人科腫瘍学会誌 22
Pages: 334-342
10026151968
Japanese Journal of Cancer Clinics 50
The Journal of the Japan Society of Gynecologic Oncology 22
Molecular Carciogenesis (In press)