Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20027-32. doi: 10.1073/pnas.1010430107. Epub 2010 Nov 1.

Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis.

Author information

  • 1University of Pittsburgh Cancer Institute and Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac effectively prevent colon cancer in humans and rodent models. However, their cellular targets and underlying mechanisms have remained elusive. We found that dietary sulindac induced apoptosis to remove the intestinal stem cells with nuclear or phosphorylated β-catenin in APC(Min/+) mice. NSAIDs also induced apoptosis in human colonic polyps and effectively removed cells with aberrant Wnt signaling. Furthermore, deficiency in SMAC, a mitochondrial apoptogenic protein, attenuated the tumor-suppressive effect of sulindac in APC(Min/+) mice by blocking apoptosis and removal of stem cells with nuclear or phosphorylated β-catenin. These results suggest that effective chemoprevention of colon cancer by NSAIDs lies in the elimination of stem cells that are inappropriately activated by oncogenic events through induction of apoptosis.

PMID:
21041628
[PubMed - indexed for MEDLINE]
PMCID:
PMC2993406
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk