Linking inflammation to cell cycle progression

Gustavo Baldassarre, Milena S. Nicoloso, Monica Schiappacassi, Emmanuel Chimienti, Barbara Belletti

Research output: Contribution to journalArticlepeer-review

Abstract

Risk of gastrointestinal cancers is closely related toincreased levels of oxidants in the balance between oxidant and anti-oxidant agents. A possible explanation ofthis epidemiological observation is the local loss of the epithelial barrier function with a focal inflammatory response. Accordingly, chronic inflammatory diseases represent well-known risk factors for cancer and on the other hand, it is known that anti-inflammatory agents, demulcents and antioxidant, markedly inhibit the development of colon cancer in animal models as well in humans. At molecular level a key role in the process that link inflammation to cellular transformation seems to be played by activation of Cyclooxygenase-2 (COX-2) together with production of Reactive Oxygen Intermediate (ROI). Both these events have been strictly linked with cell proliferation and transformation, although the intracellular pathways involved in these processes are still not completely understood. The uncontrolled proliferation, which is a landmark of cellular transformation, is accompanied by the deregulation of proteins involved in the control of cell cycle checkpoints. Altered expression and function of cyclooxygenase and nitric oxide synthase seem to influence, among others, the expression of proteins involved in the regulation of cell cycle progression. Similarly, anti-inflammatory and antioxidant agents may also act on the expression and function of several cell cycle regulating proteins. Understanding the mechanisms by which chronic inflammation contributes to genetic and epigenetic changes involved in the regulation of critical cell cycle checkpoints may help to develop more and more specific treatment strategies for reducing malignant transformation of these inflammatory diseases.

Original languageEnglish
Pages (from-to)1653-1666
Number of pages14
JournalCurrent Pharmaceutical Design
Volume10
Issue number14
DOIs
Publication statusPublished - 2004

Keywords

  • Cell cycle regulation
  • CKI
  • Colorectal cancer
  • Inflammation
  • NOS
  • Prostaglandin
  • Reactive oxygen intermediate

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

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