Home | My Profile | Contact Us
Research Trends Products  |   order gateway  |   author gateway  |   editor gateway  
Register | Forgot Password

Author Resources
 Author Gateway
 Article submission guidelines

Editor Resources
 Editor/Referee Gateway

 Regional Subscription Agents/Distributors
Current Topics in Pharmacology   Volumes    Volume 20 
The new ApoE analog DPT-Cog inhibits PI3k/Akt-dependent survival of human radio-resistant U87G glioblastoma cells
Jean-Hervé Colle, Alphonse Garcia
Pages: 33 - 37
Number of pages: 5
Current Topics in Pharmacology
Volume 20 

Copyright © 2016 Research Trends. All rights reserved

Numerous human cancers including radio-resistant human glioblastomas require a constitutive activation of the PI3K-Akt pathway for their survival. In this context the protein phosphatase-2A (PP2A) family of ser/thr protein phosphatases is a central regulator of cell homeostasis that counteracts the aberrant oncogenic PI3K survival signal. Importantly the trimeric ABαC holoenzyme, named PP2A1, specifically counteracts the aberrant oncogenic constitutively activated PI3K survival signal. In this regard we recently reported that the pharmacological activation of PP2A mediated by the sphingolipid analog FTY720 down-regulated the constitutively active PI3K/Akt pathway involved in the survival of radio-resistant U87G human glioblastoma cells. In this study, using a peptide-based drug phosphatase technology (DPT) we rational designed a new PP2A activator corresponding to an ApoE-mimetic bipartite-peptide, named DPT-Cog, that combines the cellular inactive DPT-sh1 shuttle (VKKKKIKREIKI) and the PP2A activating COG133 sequence (LRVRLASHLRK LRKRLL). We first demonstrated that this new chimeric DPT-sequence down-regulated the PI3K-Akt survival pathway and inhibited the survival of U87G cells. In addition we found that DPT-Cog decreased the growth of human glioblastoma U87G cells. Furthermore, DPT-Cog also decreased the growth of X-irradiated U87G senescent cells. In conclusion we characterized the DPT-Cog molecule, a new ApoE cog-mimetic and potential anti-tumor peptide. Our results clearly indicate that DPT-Cog counteracted PI3K survival pathways of U87G cells and is also toxic against irradiated U87G senescent cells.
View Full Article  


Buy this article
Buy this volume
Subscribe to this title
Shopping Cart

Quick Links
Search Products
Browse in Alphabetical Order : Journals
Browse by Subject Classification : Journals

Ordering Information Ordering Information
Downloadable forms Downloadable Forms