5-aminosalicylic acid interferes in the cell cycle of colorectal cancer cells and induces cell death modes

Inflamm Bowel Dis. 2010 Mar;16(3):379-89. doi: 10.1002/ibd.21086.

Abstract

Introduction: Epidemiological data suggests that 5-aminosalicylic acid (5-ASA), a nonsteroidal antiinflammatory drug used in the treatment of inflammatory bowel diseases, prevents colorectal cancer development in these patients, although the mechanisms remain incompletely understood.

Methods and results: Here we report that 5-ASA prevents growth of several colorectal cancer cell lines by interfering in the cell cycle, i.e., an S-phase and G2/M phase arrest, dependent on 5-ASA dosage and concentration, together with an increased mitotic index. In addition, prolonged cell cycle arrest by repeated 5-ASA treatment induced apoptosis and caused abnormal spindle organization leading to mitotic catastrophe, another form of cell death.

Conclusion: These observations illustrate that 5-ASA has chemopreventive and chemotherapeutic properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects*
  • Caco-2 Cells
  • Cell Division / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology*
  • Flow Cytometry
  • G2 Phase / drug effects
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Mesalamine / pharmacology*
  • Microtubule-Associated Proteins / metabolism
  • Mitosis / drug effects
  • PPAR gamma / metabolism
  • S Phase / drug effects
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / pathology
  • Survivin

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • PPAR gamma
  • Survivin
  • Mesalamine