Hello all,
I recently treated telomerase-inhibited A549 cells with 5 uM RITA, a p53 activator drug, and measured cell viability using the MTT assay. While wild type A549 experienced an expected reduction in viability, telomerase-inhibited A549 increased in viability by about 18%. It is rather unexpected to see p53 activation making these cells healthier and more viable. Would it be possible that treatment with RITA is increasing levels of replicative senescence instead of apoptosis?
The MTT assay measures viability by looking at metabolic activity of the cells. But senescent cells remain metabolically active despite having stopped proliferating, so theoretically they would appear healthy in the MTT assay as well. Therefore, would it be possible that an increase in senescence be "masking" the effect of RITA on reducing cell viability?
Thanks for your thoughts.
As you clearly mentioned, it is important that senescent cancer cells remain metabolically active despite having stopped proliferating. I would like to emphasize two critical points to discuss.
1. Senescent cancer cells tend to less depend on mitochondrial metabolism due to the dysregulation of mitophagy (the clearance of old and dysfunctional mitochondria by autophagy). This also leads to increased level of redox stress (ROS).
2. p53 activation is likely to induce metabolic reprogramming, so that MTT assay in which the amount of synthesized ATP is measured, might fail to correctly evaluate the metabolic activity.
The short answer is Yes. It depends on the cell context and treatment. In your case, it is likely that cells are able to bypass cell death.
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology
- Pharmaceuticals
- Drugs