Low dose of wortmannin reduces radiosensitivity of cells

Abstract Wortmannin is an inhibitor of PI3-kinase and acts on cultured cells at doses below 1 μM. Wortmannin also inhibits the PI3-kinase family such as ATM or DNA-PK at doses above 10 μM. There are many reports on the enhancement of cell radiosensitivity by using a high dose of wortmannin inhibiting the proteins of the PI3-kinase family. However, there have been no reports of the effects on the radiosensitivity of low doses of wortmannin inhibiting PI3-kinase. We found that low doses of wortmannin reduced the radiosensitivity of human glioblastoma cells, which had wild-type p53 . A low dose of wortmannin did not affect the accumulation of p53 and the phosphorylation of p53 at ser-15; however, a low dose reduced the induction of Waf-1 and enhanced the induction of GADD45. As the fraction of G2/M cells was reduced, however, the fraction of G1 cells was increased by a low dose of wortmannin after X-ray irradiation.