【文章名】Synthesis of A83586C analogs with potent anticancer and b-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb.
Synthesis of A83586C analogs with potent anticancer and b-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb.
作者
Hale, Karl J.;Manaviazar, Soraya;Lazarides, Linos;George, Jonathan;Walters, Marcus A.;Cai, Jiaqiang;Delisser, Vern M.;Bhatia, Gurpreet S.;Peak, S. Andrew;Dalby, Stephen M.;Lefranc, Amandine;Chen, Ying-Nan P.;Wood, Alexander W.;Crowe, Paul;Erwin, Pauline;E
[摘要]：The synthesis of three potent new antitumor agents is described: the A83586C-citropeptin hybrid (I, R = OMe), the A83586C-GE3 hybrid (I, R = H), and L-Pro-A83586C (II). Significantly, compds. I (R = OMe, H) function as highly potent inhibitors of b-catenin/TCF4 signaling within cancer cells, while simultaneously downregulating osteopontin (Opn) expression. A83586C antitumor cyclodepsipeptides also inhibit E2F-mediated transcription by downregulating E2F1 expression and inducing dephosphorylation of the oncogenic hyperphosphorylated retinoblastoma protein (pRb).
