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Oncol Rep. 2002 Jul-Aug;9(4):859-62.

Low dose of wortmannin reduces radiosensitivity of human glioblastoma cells through the p53 pathway.

Author information

1
Department of Radiation Biophysics, Radiation Effect Research Unit, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Sakamoto, Nagasaki 852-8523, Japan. okaichi@net.nagasaki-u.ac.jp

Abstract

Wortmannin is an inhibitor of PI3-kinase and acts on cultured cells at dosages below 1 microM. Wortmannin also inhibits the gene products of the PI3-kinase family such as ATM or DNA-PK at dosages above 10 microM in cultured cells. There are many reports on the enhancement of radiosensitivity by a high dose of wortmannin inhibiting the proteins of the PI3-kinase family. However, there have been no reports on the effect on radiosensitivity of low doses of wortmannin inhibiting PI3-kinase. We found that low doses of wortmannin reduced the radiosensitivity of human A172 glioblastoma cells. This effect was shown only in wild-type p53 cells, but was not shown in mutant p53 cells such as T98G or A172/248W carrying a dominant point-mutated p53 gene. This result indicates that the PI3-kinase, or another wortmannin-sensitive enzyme, may affect the signal transduction of p53. We examined the response of the p53 pathway by X-ray irradiation. A low dose of wortmannin did not affect the accumulation of p53 and the phosphorylation of p53 at ser-15, but reduced the induction of WAF1 and enhanced the induction of GADD45.

PMID:
12066222
[Indexed for MEDLINE]

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