Wortmannin-Enhanced X-Ray-Induced Apoptosis of Human T-Cell Leukemia MOLT-4 Cells Possibly through the JNK/SAPK Pathway

Abstract Tomita, M., Suzuki, N., Matsumoto, Y., Enomoto, A., Yin, H. L., Hosoi, Y., Hirano, K. and Sakai, K. Wortmannin-Enhanced X-Ray-Induced Apoptosis of Human T-Cell Leukemia MOLT-4 Cells Possibly through the JNK/SAPK Pathway. Radiat. Res. 160, 467–477 (2003). We demonstrated that enhancement of X-ray-induced apoptosis/rapid cell death by wortmannin accompanied by increased activation of JNK/SAPK in human leukemia MOLT-4 cells. Rapid cell death/apoptosis was determined either by the dye exclusion test or by the appearance of Annexin V-positive cells and cleaved PARP fragments. Enhancement was observed only at higher concentrations of wortmannin, i.e. 1 μM or more. At these high concentrations, both DNA-PK and ATM were inhibited. X-ray-induced phosphorylation of Ser 15 of p53/TP53, accumulation of both p53/TP53 and p21/WAF1/CDKN1A, and phosphorylation of XRCC4 were all suppressed. The enhancement of apoptosis/rapid cell death by wortmannin was prevented by addition of caspase inhibitors, Z-VAD-FMK or Ac...