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Exploiting Celecoxib in Cancer Therapy

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Mitochondria: The Anti- cancer Target for the Third Millennium

Abstract

Numerous studies demonstrate that the non-steroidal anti-inflammatory drug (NSAID) Celecoxib is an attractive lead compound for cancer therapy: Epidemiological studies suggest a lower incidence of colonic polyps in patients with the hereditary familiary adenomatous polyposis (FAP) syndrome and a decreased risk for colorectal, skin and other cancers upon continuous uptake of Celecoxib or related compounds. Moreover, preclinical investigations demonstrate promising anti-tumour activity of Celecoxib in a variety of human tumours. Celecoxib not only interferes with tumour initiation and tumour cell growth in vitro and in vivo but also increases the sensitivity of tumour cells to chemotherapy, radiotherapy, or chemoradiotherapy.

Cell cycle arrest, induction of apoptosis and anti-angiogenic effects contribute to the antineoplastic effects of Celecoxib. This chapter will focus on the molecular mechanisms of Celecoxib-induced apoptosis, in particular the ability of Celecoxib to activate the mitochondrial death pathway and to interfere with specific members of the Bcl-2 protein family and the apoptosis regulator Survivin. Moreover, the role of cyclooxygenase-2 (COX-2) in the regulation of Celecoxib-induced apoptosis will be discussed. Finally, some clinical aspects of the use of Celecoxib in cancer therapy will be highlighted.

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Acknowledgements

The work in the author’s laboratory was supported by grants from the German Research Foundation (DFG; GRK1739), the Wilhelm-Sander-Stiftung 2005.143.1, and the Deutsche Krebshilfe/Mildred-Scheel-Stiftung (107388).

Conflict of interest: Pharmacia/Pfizer kindly provided Celecoxib for the studies performed by the author’s laboratory.

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  1. Department of Molecular Cell Biology, Institute of Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, Virchowstrasse 173, 45122, Essen, Germany

    Verena Jendrossek

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Correspondence to Verena Jendrossek .

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Editors and Affiliations

  1. School of Medical Science, Griffith University, Southport, Queensland, Australia

    Jiri Neuzil

  2. School of Medicine, National University of Singapore, Singapore, Singapore

    Shazib Pervaiz

  3. Institute for Experimental Cancer Research in Pediatrics, Goethe University, Frankfurt, Germany

    Simone Fulda

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Jendrossek, V. (2014). Exploiting Celecoxib in Cancer Therapy. In: Neuzil, J., Pervaiz, S., Fulda, S. (eds) Mitochondria: The Anti- cancer Target for the Third Millennium. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8984-4_5

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