Exploiting celecoxib in cancer therapy

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.