Mode of Action of Aspirin as a Chemopreventive Agent

  • Melania Dovizio
  • Annalisa Bruno
  • Stefania Tacconelli
  • Paola Patrignani
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 191)


Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. The finding of aspirin benefit at low-doses given once daily, used for cardioprevention, locates the antiplatelet effect of aspirin at the center of its antitumor efficacy. In fact, at low-doses, aspirin acts mainly by an irreversible inactivation of platelet cyclooxygenase (COX)-1 in the presystemic circulation, which translates into a long-lasting inhibition of platelet function. Given the short half-life of aspirin in the human circulation(approximately 20 min) and the capacity of nucleated cells to resynthesize the acetylated COX-isozyme(s), it seems unlikely that a nucleated cell could be the target of aspirin chemoprevention. These findings convincingly suggest that colorectal cancer and atherothrombosis may share a common mechanism of disease, i.e. platelet activation in response to epithelial(in tumorigenesis) and endothelial(in tumorigenesis and atherothrombosis) injury. Activated platelets may also enhance the metastatic potential of cancer cells (through a direct interaction and/or the release of soluble mediators or exosomes) at least in part by inducing the overexpression of COX-2. COX-independent mechanisms of aspirin, such as the inhibition of NF-kB signaling and Wnt/β-catenin signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemopreventive effects. However, their relevance remains to be demonstrated in vivo at clinical doses.


Familial Adenomatous Polyposis Chemopreventive Effect Irreversible Inactivation Serum TXB2 Washed Human Platelet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



15R-hydroxyeicosapentaenoic acid




Adenosine diphosphate


Apoptotic protease activating factor-1


Arachidonic acid


Colorectal cancer




Epidermal growth factor receptor


Extracellular signal-regulated kinase


Familial adenomatous polyposis


Fibroblast growth factor


Insulin-like growth factor




Bacterial endotoxin




Microsomal PGE2 synthase-1


Natural killer


Nonsteroidal anti-inflammatory drug


Nuclear factor kappa B


Platelet-derived growth factor


Platelet-derived growth factor






Protein kinase C






T-cell factor (Tcf)/lymphoid enhancer factor




Tissue inhibitor of metalloproteinases


Tumor cell-induced platelet aggregation


TXA2 synthase


Vascular endothelial growth factor



This work was supported by research funding from the Associazione Italiana per la Ricerca sul Cancro (AIRC) to Paola Patrignani. We would like to thank, for fruitful discussions and suggestions, Dr Carlo Patrono (Catholic University, Rome, Italy), Luis A Garcia Rodriguez (CEIFE, Madrid, Spain) and Angel Lanas (University of Zaragoza, Spain). We apologize to our colleagues for not being able to reference all primary work due to space limitations.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Melania Dovizio
    • 1
  • Annalisa Bruno
    • 2
  • Stefania Tacconelli
    • 1
  • Paola Patrignani
    • 1
  1. 1.Center of Excellence on Aging (CeSI) and Department of Neuroscience and ImagingG. d’Annunzio University, School of MedicineChietiItaly
  2. 2.Center of Excellence on Aging (CeSI) and Department of Medicine and AgingG. d’Annunzio University, School of MedicineChietiItaly

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