Mode of action of aspirin as a chemopreventive agent

Recent Results Cancer Res. 2013;191:39-65. doi: 10.1007/978-3-642-30331-9_3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Aspirin / pharmacokinetics
  • Aspirin / pharmacology*
  • Blood Platelets / physiology
  • Colorectal Neoplasms / prevention & control*
  • Cyclooxygenase Inhibitors / pharmacology
  • Humans
  • Prostaglandin-Endoperoxide Synthases / physiology

Substances

  • Anticarcinogenic Agents
  • Cyclooxygenase Inhibitors
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin