Nonsteroidal anti-inflammatory drug sulindac sulfide suppresses structural protein Nesprin-2 expression in colorectal cancer cells
Document Type
Article
Publication Date
1-1-2014
Department
Department of Mechanical Engineering-Engineering Mechanics
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 immunohistochemistry 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, immunohistochemistry 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.
Publication Title
Biochimica et Biophysica Acta - General Subjects
Recommended Citation
Liggett, J.,
Choi, C.,
Donnell, R.,
Kihm, K.,
Kim, J.,
Min, K.,
Noegel, A.,
&
Baek, S.
(2014).
Nonsteroidal anti-inflammatory drug sulindac sulfide suppresses structural protein Nesprin-2 expression in colorectal cancer cells.
Biochimica et Biophysica Acta - General Subjects,
1840(1), 322-331.
http://doi.org/10.1016/j.bbagen.2013.09.032
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/2438
Publisher's Statement
© 2013 Elsevier B.V. Publisher’s version of record: https://doi.org/10.1016/j.bbagen.2013.09.032