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Increase in intracellular PGE2 induces apoptosis in Bax-expressing colon cancer cell
Lisenn Lalier1, François Pedelaborde, Christophe Braud
1Département de Biologie Oncologique, Centre de Lutte Contre le Cancer René Gauducheau, Bd J, Monod, 44805 Nantes, Saint Herblain Cedex, France. lisenn.lalier@univ-nantes.fr
Background:
NSAIDs exhibit protective properties towards some cancers, especially colon cancer. Yet, it is not clear how they play their protective role. PGE2 is generally shown as the only target of the NSAIDs anticancerous activity. However, PGE2 known targets become more and more manifold, considering both the molecular pathways involved and the target cells in the tumour. The role of PGE2 in tumour progression thus appears complex and multipurpose.
Methods:
To gain understanding into the role of PGE2 in colon cancer, we focused on the activity of PGE2 in apoptosis in colon cancer cell lines.
Results:
We observed that an increase in intracellular PGE2 induced an apoptotic cell death, which was dependent on the expression of the proapoptotic protein Bax. This increase was induced by increasing PGE2 intracellular concentration, either by PGE2 microinjection or by the pharmacological inhibition of PGE2 exportation and enzymatic degradation.
Conclusions:
We present here a new sight onto PGE2 in colon cancer cells opening the way to a new prospective therapeutic strategy in cancer, alternative to NSAIDs.
Insights
Increasing prostaglandin E2 (PGE2) levels within colon cancer cells triggers apoptosis, mediated by the Bax protein. This finding offers a novel therapeutic strategy for colon cancer beyond NSAIDs.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Non-steroidal anti-inflammatory drugs (NSAIDs) show protective effects against certain cancers, notably colon cancer.
- The precise mechanisms underlying NSAIDs' anticancer activity are not fully understood, with prostaglandin E2 (PGE2) often cited as the primary target.
- PGE2's role in tumor progression is complex, involving diverse molecular pathways and cellular targets.
Purpose of the Study:
- To investigate the specific role of prostaglandin E2 (PGE2) in inducing apoptosis within colon cancer cell lines.
- To elucidate the molecular mechanisms by which PGE2 influences colon cancer cell death.
Main Methods:
- Utilizing colon cancer cell lines to study the effects of PGE2.
- Manipulating intracellular PGE2 concentrations through microinjection and pharmacological inhibition of its export and degradation pathways.
- Assessing the impact of altered PGE2 levels on apoptotic cell death and the expression of key apoptotic proteins.
Main Results:
- An increase in intracellular PGE2 concentration was found to induce apoptotic cell death in colon cancer cells.
- This PGE2-induced apoptosis was dependent on the expression of the proapoptotic protein Bax.
- Elevated intracellular PGE2 levels were achieved via direct microinjection or by inhibiting PGE2's enzymatic degradation and cellular export.
Conclusions:
- Prostaglandin E2 (PGE2) plays a direct role in inducing apoptosis in colon cancer cells.
- The proapoptotic effect of PGE2 is mediated through the Bax protein.
- These findings suggest a novel therapeutic strategy for colon cancer targeting intracellular PGE2 levels, offering an alternative to traditional NSAID-based approaches.
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