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The new Sulindac derivative IND 12 reverses Ras-induced cell transformation

Ioanna-Maria Karaguni, Peter Herter, Philip Debruyne, Slava Chtarbova, Alice Kasprzynski, Ulrike Herbrand, M-Reza Ahmadian, Karl-Heinz Glüsenkamp, Günther Winde, Marcus Mareel, et al. (2002) CANCER RESEARCH. 62(6). p.1718-1723
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
KINASE, DIFFERENTIATION, FAMILIAL ADENOMATOUS POLYPOSIS, COLON-CANCER CELLS, EPITHELIAL-CELLS, COLORECTAL-CANCER, APOPTOSIS, INVASION, CARCINOGENESIS, ADHESION
journal title
CANCER RESEARCH
Cancer Res.
volume
62
issue
6
pages
1718 - 1723
Web of Science type
Article
Web of Science id
000174560200022
JCR category
ONCOLOGY
JCR impact factor
8.318 (2002)
JCR rank
7/112 (2002)
JCR quartile
1 (2002)
ISSN
0008-5472
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
151771
handle
http://hdl.handle.net/1854/LU-151771
alternative location
http://cancerres.aacrjournals.org/content/62/6/1718
date created
2004-01-14 13:38:00
date last changed
2016-12-19 15:37:50
@article{151771,
  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.},
  author       = {Karaguni, Ioanna-Maria and Herter, Peter and Debruyne, Philip and Chtarbova, Slava and Kasprzynski, Alice and Herbrand, Ulrike and Ahmadian, M-Reza and Gl{\"u}senkamp, Karl-Heinz and Winde, G{\"u}nther and Mareel, Marcus and M{\"o}r{\"o}y, Tarik and M{\"u}ller, Oliver},
  issn         = {0008-5472},
  journal      = {CANCER RESEARCH},
  keyword      = {KINASE,DIFFERENTIATION,FAMILIAL ADENOMATOUS POLYPOSIS,COLON-CANCER CELLS,EPITHELIAL-CELLS,COLORECTAL-CANCER,APOPTOSIS,INVASION,CARCINOGENESIS,ADHESION},
  language     = {eng},
  number       = {6},
  pages        = {1718--1723},
  title        = {The new Sulindac derivative IND 12 reverses Ras-induced cell transformation},
  url          = {http://cancerres.aacrjournals.org/content/62/6/1718},
  volume       = {62},
  year         = {2002},
}

Chicago
Karaguni, Ioanna-Maria, Peter Herter, Philip Debruyne, Slava Chtarbova, Alice Kasprzynski, Ulrike Herbrand, M-Reza Ahmadian, et al. 2002. “The New Sulindac Derivative IND 12 Reverses Ras-induced Cell Transformation.” Cancer Research 62 (6): 1718–1723.
APA
Karaguni, I.-M., Herter, P., Debruyne, P., Chtarbova, S., Kasprzynski, A., Herbrand, U., Ahmadian, M.-R., et al. (2002). The new Sulindac derivative IND 12 reverses Ras-induced cell transformation. CANCER RESEARCH, 62(6), 1718–1723.
Vancouver
1.
Karaguni I-M, Herter P, Debruyne P, Chtarbova S, Kasprzynski A, Herbrand U, et al. The new Sulindac derivative IND 12 reverses Ras-induced cell transformation. CANCER RESEARCH. 2002;62(6):1718–23.
MLA
Karaguni, Ioanna-Maria, Peter Herter, Philip Debruyne, et al. “The New Sulindac Derivative IND 12 Reverses Ras-induced Cell Transformation.” CANCER RESEARCH 62.6 (2002): 1718–1723. Print.