Related Experiment Video

Updated: Jul 10, 2026

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
07:22

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Published on: March 28, 2013

PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs

T C He1, T A Chan, B Vogelstein

  • 1Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, Maryland 21231, USA.

Cell
|November 11, 1999
PubMed

Insights

The tumor suppressor APC normally represses PPARdelta in colorectal cancer (CRC). Non-steroidal anti-inflammatory drugs (NSAIDs) like sulindac inhibit this gene, potentially blocking CRC tumor growth.

Area of Science:

  • Molecular biology
  • Cancer research
  • Genetics

Background:

  • Colorectal cancer (CRC) is a significant health concern.
  • The adenomatous polyposis coli (APC) gene plays a crucial role in CRC development.
  • Peroxisome proliferator-activated receptors (PPARs) are involved in cellular processes and cancer.

Purpose of the Study:

  • To investigate the relationship between APC and PPARdelta in colorectal cancer.
  • To explore the potential role of PPARdelta as a target for non-steroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention.

Main Methods:

  • Global gene expression profiling in human colorectal cancer cells.
  • Analysis of PPARdelta promoter activity using reporter assays.
  • Assessing the effect of sulindac on PPARdelta activity and binding.

Main Results:

  • PPARB was identified as a target of APC, with PPARdelta expression elevated in CRCs and repressed by APC.
  • APC's repression of PPARdelta is mediated by beta-catenin/Tcf-4-responsive elements in the PPARdelta promoter.
  • The NSAID sulindac repressed PPARdelta activity and disrupted its DNA binding, suggesting a mechanism for chemoprevention.

Conclusions:

  • APC normally regulates PPARdelta expression in colorectal cancer cells.
  • NSAIDs, such as sulindac, inhibit tumorigenesis by targeting and repressing PPARdelta.
  • These findings highlight a novel mechanism for NSAID-mediated chemoprevention in CRC.

More Related Videos

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader07:13

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader

Published on: May 24, 2024

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Related Concept Videos

G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Drug-Receptor Interaction: Antagonist01:28

Drug-Receptor Interaction: Antagonist

An antagonist is a drug that binds strongly to a receptor without activating it. An antagonist prevents other molecules, such as neurotransmitters or hormones, from binding to the receptor and triggering a cellular response. Such interaction effectively hinders the normal physiological processes mediated by the receptor, resulting in various pharmacological effects depending on the specific receptor targeted.
Antagonists can be classified as competitive or noncompetitive based on their...
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...