contribution of Chk1 and Chk2 to the G2 arrest caused naphthalimide, we compared the phosphorylation of Chk1 and Chk2. In all groups treated with different Top2 inhibitors for 24 hours, Chk2 protein was phosphorylated, such as by increasing p Chk2, Factor Xa review which was tats Chlich by pretreatment with specified ATM siRNA1 thwarted. Under the same experimental treatment, however, was not detectable phosphorylated Chk1 in response to both R16 and amonafide, although Chk1 is usually by treatment with VP16, which was also prevented by pretreatment with ATM siRNA1 phosphorylated. In addition, we also have best Firmed that naphthalimides induced degradation of Chk1 has been reported in our previous article.
Our data demonstrate that Chk1 and Chk2 are differentially phosphorylated by ATM in response to naphthalimides. Discussion and amonafide R16 Both are from others Hnlichen naphthalimide for their anti-cancer activity Tonnes. However, the molecular mechanisms remain not YOUR BIDDING MLN8054 clarified Rt. We showed in detail that both R16 and amonafide human target Top2, thus generating Bezirksschulr-run DNA in HL-60 cells, which have led to the arrest and G2 M. We also showed that R16 induced Chk1 degradation by the ubiquitin-proteasome pathway that its anti-cancer activity of t Posts gt In this study we have further clarified their specific cell cycle arrest at G2 phase rt And, more importantly, established a m Adjusted association between DNA and molecular CSD G2 arrest induced by R16 and amonafide.
Properly define a cell cycle arrest of cancer drugs is important because it helps Aufkl Tion of the mechanisms of its anti-cancer activity Ten. Figure 6 R16 induced phosphorylation of Chk1 and Chk2 differential. Chk2 phosphorylation by R16 on loan St was blocked by the ATM siRNA1. HCT116 cells were treated with R16, amonafide, or VP16 at the indicated concentrations for 24 hours after they treated with 100 nM ATM siRNA1 transfected for 24 hours. Subsequently End, the cells were subjected to Western blot analysis for Chk1, Chk2, Chk1 and Chk2 pp. The illustrations were repr Sentative for three independent Independent experiments. Schematic representation of the mechanistic link m Possible between inhibition of Top2 and G2 arrest caused by naphthalimides. Induce G2 arrest in 1232 naphthalimides via ATM Chk2 pathway Zhu et al.
Flight neoplasia. 11, No. 11, 2009 In addition, the specificity of t of cancer drugs in a cell cycle arrest as a significant basis used for the combination therapy. With the specific marker phosphorylated histone H3 mitosis and MPM 2, we have shown that the cells small M-phase in R16 and amonafide treated groups HCT116 cells, which the G2 arrest induced by these two compounds best CONFIRMS had. The control point G2 is often used by DNA-Sch Enabled the CBD. Therefore best Firmed that we R16 and amonafide CSD-induced DNA HCT116 cells revealed that both cellular connections Level of phosphorylated histone H2AX rer improved γ and causes the generation of comet tails, as they did in the HL 60th After the generation of DNA-CBD was ATM, the primary Rsensor of DSBs DNA by its phosphorylation on serine 1981 to R16 or activated amonafidetreated cells. The pan phosphoinositide 3-kinase inhibitor caffeine and its specific siRNA but not ATM ATR siRNA, the G2 arrest through R16 and amonafide rescue loan St, a urs Chlichen relationship between ATM activation and G2 arrest in t