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Updated: May 25, 2026

Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)
12:37

Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)

Published on: September 11, 2012

Acute sensitization of colon cancer cells to inflammatory cytokines by prophase arrest

Anton Kuratnik1, Virginia E Senapati, Rajeev Verma

  • 1Department of Molecular and Cell Biology, 91 North Eagleville Road, University of Connecticut, Storrs, CT 06269, United States.

Biochemical Pharmacology
|February 7, 2012
PubMed

Insights

Histone deacetylase inhibitors sensitize colon cancer cells to inflammatory cytokines like TNF and TRAIL by inducing prophase arrest. This finding offers potential new strategies for colon cancer therapy and prevention.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Cell Biology

Background:

  • Colon cancer cells thrive in inflammatory tumor environments.
  • Developing strategies to enhance cancer cell sensitivity to inflammatory cytokines is crucial for effective therapy.

Purpose of the Study:

  • To investigate how colon cancer cells survive within the tumor's inflammatory milieu.
  • To identify therapeutic agents that sensitize colon cancer cells to inflammatory cytokines, such as tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL).

Main Methods:

  • Analysis of chemopreventive and therapeutic agents, focusing on histone deacetylase (HDAC) inhibitors.
  • In vivo studies using AOM-induced colon tumors.
  • Cell cycle analysis and time-lapse imaging.
  • siRNA analysis targeting Aurora kinases.

Main Results:

  • HDAC inhibitors, specifically SAHA (suberoylanilide hydroxamic acid), effectively sensitize colon cancer cells to TNF- and TRAIL-mediated apoptosis.
  • SAHA administration enhances apoptosis in AOM-induced colon tumors, which exhibit elevated TNF levels.
  • SAHA-induced prophase arrest closely correlates with TNF- or TRAIL-induced apoptosis.
  • The Aurora kinase inhibitor VX680 also sensitizes cells to TNF and TRAIL, with Aurora kinase A identified as the key mediator.

Conclusions:

  • Agents that induce prophase arrest may sensitize cancer cells to inflammatory cytokines like TNF.
  • Circumvention of early mitotic checkpoints may contribute to cancer cell survival in inflammatory tumor microenvironments.
  • These findings suggest novel therapeutic and preventive strategies for colon cancer by targeting inflammatory pathways and cell cycle regulation.

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