Universität zu Köln

Liggett, Jason L., Choi, Chang Kyoung, Donnell, Robert L. ORCID: 0000-0002-6778-954X, Kihm, Kenneth D., Kim, Jong-Sik, Min, Kyung-Won ORCID: 0000-0002-8718-3588, Noegel, Angelika Anna and Baek, Seung Joon (2014). Nonsteroidal anti-inflammatory drug sulindac sulfide suppresses structural protein Nesprin-2 expression in colorectal cancer cells. Biochim. Biophys. Acta-Gen. Subj., 1840 (1). S. 322 - 332. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1872-8006

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Abstract

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known for treating inflammatory disease and have been reported to have anti-tumorigenic effects. Their mechanisms are not fully understood, but both cyclooxygenase (COX) dependent and independent pathways are involved. Our goal was to shed further light on COX-independent activity. Methods: Human colorectal cancer cells were observed under differential interference contrast microscopy (DICM), fluorescent microscopy, and micro-impedance measurement. Microarray analysis was performed using HCT-116 cells treated with sulindac sulfide (SS). PCR and Western blots were performed to confirm the microarray data and immunohistochemisty was performed to screen for Nesprin-2 expression. Micro-impedance was repeating including Nesprin-2 knock-down by siRNA. Results: HCT-116 cells treated with SS showed dramatic morphological changes under DICM and fluorescent microscopy, as well as weakened cellular adhesion as measured by micro-impedance. Nesprin-2 was selected from two independent microarrays, based on its novelty in relation to cancer and its role in cell organization. SS diminished Nesprin-2 mRNA expression as assessed by reverse transcriptase and real time PCR. Various other NSAIDs were also tested and demonstrated that inhibition of Nesprin-2 mRNA was not unique to SS. Additionally, immunohistochernistry showed higher levels of Nesprin-2 in many tumors in comparison with normal tissues. Further micro-impedance experiments on cells with reduced Nesprin-2 expression showed a proportional loss of cellular adhesion. Conclusions: Nesprin-2 is down-regulated by NSAIDs and highly expressed in many cancers. General significance: Our data suggest that Nesprin-2 may be a potential novel oncogene in human cancer cells and NSAIDs could decrease its expression. (C) 2013 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Liggett, Jason L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Chang Kyoung UNSPECIFIED UNSPECIFIED UNSPECIFIED Donnell, Robert L. UNSPECIFIED orcid.org/0000-0002-6778-954X UNSPECIFIED Kihm, Kenneth D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Jong-Sik UNSPECIFIED UNSPECIFIED UNSPECIFIED Min, Kyung-Won UNSPECIFIED orcid.org/0000-0002-8718-3588 UNSPECIFIED Noegel, Angelika Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Baek, Seung Joon UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-450876
DOI:	10.1016/j.bbagen.2013.09.032
Journal or Publication Title:	Biochim. Biophys. Acta-Gen. Subj.
Volume:	1840
Number:	1
Page Range:	S. 322 - 332
Date:	2014
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1872-8006
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTERFERENCE REFLECTION MICROSCOPY; BIOELECTRICAL-IMPEDANCE ASSAY; NUCLEAR-ENVELOPE; CYCLOOXYGENASE INHIBITION; ACTIN CYTOSKELETON; MONITOR CHANGES; TISSUE-CULTURE; COLON; APOPTOSIS; PREVENTION Multiple languages Biochemistry & Molecular Biology; Biophysics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45087