Related Experiment Video

Updated: Jun 24, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

Cyclooxygenase inhibitors induce colon cancer cell apoptosis Via PPARdelta --> 14-3-3epsilon pathway

Kenneth K Wu1, Jun-Yang Liou

  • 1National Health Research Institutes, Zhunan, Taiwan.

Methods in Molecular Biology (Clifton, N.J.)
|April 7, 2009
PubMed

Insights

Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors induce colon cancer cell apoptosis by suppressing PPARdelta signaling, reducing 14-3-3epsilon, and increasing Bad-induced mitochondrial cell death.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIBs) are known to induce apoptosis in cancer cells through various signaling pathways.
  • Evidence suggests these drugs induce colon cancer cell apoptosis by suppressing peroxisome proliferator-activated receptor delta (PPARdelta) via inhibition of COX-2-derived prostacyclin (PGI2).
  • PGI2 normally activates PPARdelta, leading to its binding to PPAR response elements (PPRE) in target genes, including 14-3-3epsilon.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which NSAIDs and COXIBs induce apoptosis in colon cancer cells.
  • To investigate the role of the PPARdelta signaling pathway and its downstream targets, such as 14-3-3epsilon, in mediating the anti-cancer effects of these drugs.

Main Methods:

  • The study involved analyzing the effects of NSAIDs and COXIBs on PPARdelta activity, PGI2 production, and the expression of 14-3-3epsilon and Bad in colon cancer cells.
  • Investigated the impact of PPARdelta suppression on the interaction between 14-3-3epsilon and Bad, and subsequent effects on mitochondrial apoptosis.

Main Results:

  • NSAIDs and COXIBs were found to block PGI2 production, leading to reduced PPARdelta DNA binding activity and abrogated 14-3-3epsilon upregulation.
  • COX-2 inhibitors were also shown to suppress PPARdelta expression.
  • Suppression of PPARdelta resulted in decreased 14-3-3epsilon levels, reduced sequestration of Bad, and consequently, enhanced Bad-induced apoptosis via the mitochondrial death pathway.

Conclusions:

  • NSAIDs and COXIBs promote colon cancer cell apoptosis by inhibiting the PGI2/PPARdelta/14-3-3epsilon signaling axis.
  • The downregulation of PPARdelta and subsequent reduction in 14-3-3epsilon enhance the mitochondrial apoptosis pathway by increasing the availability of Bad.
  • These findings highlight a critical mechanism underlying the anti-cancer effects of NSAIDs and COXIBs in colon cancer.

More Related Videos

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

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...