wangqian Pokročilý
Počet príspevkov : 115 Registration date : 28.11.2013
| Predmet: The amount and purity of total RNA for each sample was estimated by spectrophot Po február 17, 2014 8:36 am | |
| The signals were processed using Genelevel RMA Sketch algo rithm with following software: Affymetrix Expression Console 1. 1 software. Comparison analyses INNO-406 分子量 were car ried out with a T Test. Statistical analysis Statistical analyses were performed using the Statistical Package for Social Sciences program, version 15 with a Mann Whitney U Test for tumor growth, microvessel density data and wound assays and with the unpaired Student t test with Welch correction for proliferation experiments. Prob ability value 0. 05 was considered statistically significant. API 1 is a recently iden tified novel Akt inhibitor. It inhibits Akt activity through binding to the pleckstrin homology domain of Akt and blocking its membrane translocation.<br><br> API 1 possesses promising Lapatinib 価格 anticancer activity, evidenced by its ability to suppress cell growth, induce apoptosis and inhibit the growth of cancer xenografts, particularly those with acti vated Akt, in nude mice. We have recently shown that API 1 facilitates c FLIP degradation, induces apoptosis and enhances tumor necrosis factor related apoptosis inducing ligand induced apoptosis in human non small cell lung cancer cells. c FLIP degradation clearly contributes to the enhancement of TRAIL induced apoptosis by API 1. However, the mechanisms by which API 1 induces apoptosis in cancer cells and the additional mechanisms accounting for API 1 mediated augmentation of TRAIL induced apoptosis are largely unknown.<br><br> In addition to the extrinsic death receptor mediated apop totic pathway, which is characterized by the oligomerization of cell surface death receptors and activation of caspase 8, the intrinsic apoptotic pathway that involves the disruption of mitochondrial membranes, release of cytochrome c and activation of caspase 9 is another critical apoptotic mechan ism. It is known buy LY2109761 that the intrinsic apoptotic pathway is negatively regulated by anti apoptotic Bcl 2 family mem bers and inhibitor of apoptosis proteins. In general, down regulation of these anti apoptotic proteins can trigger apoptosis or augment TRAIL induced apoptosis. Among the anti apoptotic Bcl 2 family members, Mcl 1 is known to be a short lived protein that undergoes ubiquitination proteasome mediated degradation. One degradation mechanism involves glycogen synthase kinase 3, which phosphorylates Mcl 1 at S159, triggering Mcl 1 degradation.<br><br> It has been suggested that Mcl 1 phosphorylation at S159 facilitates the association of Mcl 1 with the E3 ligase B transducin repeats containing protein, resulting in B TrCP mediated ubiquiti nation and degradation of Mcl 1. Recently two studies have suggested that phosphorylation at S159 enhances the association of Mcl 1 with the E3 ligase F box WD repeat containing protein 7, resulting in FBXW7 mediated ubiquitination and degradation of Mcl 1. In this study, we focused on revealing mechanisms by which API 1 induces apoptosis of cancer cells and un covered GSK3 dependent Mcl 1 degradation as a critical mechanism accounting for induction of apoptosis by API 1. This mechanism also contributes to augmenta tion of TRAIL induced apoptosis by API 1. Methods Reagents API 1 was obtained from the National Cancer Institute. MK2206 was pur chased from Active Biochem. | |
|