English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  The new Sulindac derivative IND 12 reverses Ras-induced cell transformation

Karaguni, I.-M., Herter, P., Debruyne, P., Chtarbova, S., Kasprzynski, A., Herbrand, U., et al. (2002). The new Sulindac derivative IND 12 reverses Ras-induced cell transformation. Cancer Research, 62(6): 1, pp. 1718-1723. Retrieved from http://cancerres.aacrjournals.org/cgi/content/abstract/62/6/1718.

Item is

Basic

show hide
Genre: Journal Article
Alternative Title : Cancer Res.

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Karaguni, Ioanna-Maria1, Author
Herter, Peter1, Author
Debruyne, Philip, Author
Chtarbova, Slava2, Author           
Kasprzynski, Alice1, Author
Herbrand, Ulrike1, Author
Ahmadian, Mohammad Reza3, Author           
Glüsenkamp, Karl-Heinz, Author
Winde, Günther, Author
Mareel, Marc, Author
Möröy, Tarik, Author
Müller, Oliver3, Author           
Affiliations:
1Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753286              
2Abt. IV: Chemische Biologie, Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753290              
3Sonstige Wissenschaftliche Organisationseinheiten, Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753294              

Content

show
hide
Free keywords: -
 Abstract: The nonsteroidal anti-inflammatory drug Sulindac has chemopreventive and antitumorigenic properties. Its metabolites induce apoptosis and inhibit signaling pathways critical for malignant transformation, including the Ras pathway. Here we show that the new Sulindac derivative IND 12 reverses the phenotype of Ras-transformed MDCK-f3 cells and restores an untransformed epithelioid morphology characterized by growth in monolayers with regular cell-cell adhesions. Moreover, IND 12 treatment induces the expression at membranes of the cell adhesion protein E-cadherin and increases the level of the E- cadherin-bound beta-catenin. As a consequence, IND 12-treated MDCK-f3 cells lose their invasion capacity and regain the ability to aggregate. In the presence of IND 12, MDCK-f3 cells show regenerated expression and activity ratios of the small GTPases Rac and Rho normally found in untransformed MDCK cells. Strikingly, IND 12 treatment decreases the levels of phosphorylated mitogen-activated protein kinases, which are downstream substrates of the Ras-regulated Raf/mitogen- activated protein kinase pathway, and the level of Ras-induced activation of gene expression. Our findings identify a novel drug with high potential in cancer therapy by targeting Ras- induced cell transformation.

Details

show
hide
Language(s): eng - English
 Dates: 2002-03-15
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Cancer Research
  Alternative Title : Cancer Res.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 62 (6) Sequence Number: 1 Start / End Page: 1718 - 1723 Identifier: -