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Article

Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo

  • Authors:
    • Ann-Katrin Claudius
    • Chandra S. Kankipati
    • Rajagopal S. Kilari
    • Sadiya Hassan
    • Kerry Guest
    • Steven T. Russell
    • Chris J. Perry
    • Lesley A. Stark
    • Iain D. Nicholl
  • View Affiliations / Copyright

    Affiliations: Edinburgh Cancer Research Centre and MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK, The Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK, Life and Health Sciences, Aston Triangle, Aston University, Birmingham B4 7ET, UK
  • Pages: 1670-1680
    |
    Published online on: July 31, 2014
       https://doi.org/10.3892/or.2014.3373
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Abstract

Substantial evidence indicates that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have potential as chemopreventative/therapeutic agents. However, these agents cannot be universally recommended for prevention purposes due to their potential side-effect profiles. Here, we compared the growth inhibitory and mechanistic activity of aspirin to two novel analogues, diaspirin (DiA) and fumaryl diaspirin (F-DiA). We found that the aspirin analogues inhibited cell proliferation and induced apoptosis of colorectal cancer cells at significantly lower doses than aspirin. Similar to aspirin, we found that an early response to the analogues was a reduction in levels of cyclin D1 and stimulation of the NF-κB pathway. This stimulation was associated with a significant reduction in basal levels of NF-κB transcriptional activity, in keeping with previous data for aspirin. However, in contrast to aspirin, DiA and F-DiA activity was not associated with nucleolar accumulation of RelA. For all assays, F-DiA had a more rapid and significant effect than DiA, identifying this agent as particularly active against colorectal cancer. Using a syngeneic colorectal tumour model in mice, we found that, while both agents significantly inhibited tumour growth in vivo, this effect was particularly pronounced for F-DiA. These data identify two compounds that are active against colorectal cancer in vitro and in vivo. They also identify a potential mechanism of action of these agents and shed light on the chemical structures that may be important for the antitumour effects of aspirin.
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Copy and paste a formatted citation
Spandidos Publications style
Claudius A, Kankipati CS, Kilari RS, Hassan S, Guest K, Russell ST, Perry CJ, Stark LA and Nicholl ID: Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo. Oncol Rep 32: 1670-1680, 2014.
APA
Claudius, A., Kankipati, C.S., Kilari, R.S., Hassan, S., Guest, K., Russell, S.T. ... Nicholl, I.D. (2014). Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo. Oncology Reports, 32, 1670-1680. https://doi.org/10.3892/or.2014.3373
MLA
Claudius, A., Kankipati, C. S., Kilari, R. S., Hassan, S., Guest, K., Russell, S. T., Perry, C. J., Stark, L. A., Nicholl, I. D."Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo". Oncology Reports 32.4 (2014): 1670-1680.
Chicago
Claudius, A., Kankipati, C. S., Kilari, R. S., Hassan, S., Guest, K., Russell, S. T., Perry, C. J., Stark, L. A., Nicholl, I. D."Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo". Oncology Reports 32, no. 4 (2014): 1670-1680. https://doi.org/10.3892/or.2014.3373
Copy and paste a formatted citation
x
Spandidos Publications style
Claudius A, Kankipati CS, Kilari RS, Hassan S, Guest K, Russell ST, Perry CJ, Stark LA and Nicholl ID: Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo. Oncol Rep 32: 1670-1680, 2014.
APA
Claudius, A., Kankipati, C.S., Kilari, R.S., Hassan, S., Guest, K., Russell, S.T. ... Nicholl, I.D. (2014). Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo. Oncology Reports, 32, 1670-1680. https://doi.org/10.3892/or.2014.3373
MLA
Claudius, A., Kankipati, C. S., Kilari, R. S., Hassan, S., Guest, K., Russell, S. T., Perry, C. J., Stark, L. A., Nicholl, I. D."Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo". Oncology Reports 32.4 (2014): 1670-1680.
Chicago
Claudius, A., Kankipati, C. S., Kilari, R. S., Hassan, S., Guest, K., Russell, S. T., Perry, C. J., Stark, L. A., Nicholl, I. D."Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo". Oncology Reports 32, no. 4 (2014): 1670-1680. https://doi.org/10.3892/or.2014.3373
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