Journal
BLOOD
Volume 122, Issue 14, Pages 2402-2411Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-01-478651
Keywords
-
Categories
Funding
- la Fondation Association pour la Recherche sur le Cancer
- la Fondation de France
- le Centre Scientifique de Monaco
- l'Agence Nationale de la Recherche [ANR-09-JCJC-0003]
- la Ville de Nice
- la Fondation pour la Recherche Medicale
- Leukemia Foundation Australia
- Australian National Health and Medical Research Council (Australia RD Wright Biomedical) [CDA 406675]
- Victorian Cancer Agency
- Cancer Council Victoria (Sir Edward Dunlop Research Fellow)
- Institut national de la sante et de la recherche medicale
- Centre Hospitalier Universitaire de Nice
- Agence Nationale de la Recherche (ANR) [ANR-09-JCJC-0003] Funding Source: Agence Nationale de la Recherche (ANR)
Ask authors/readers for more resources
Caloric restriction (CR) is proposed to decrease tumorigenesis through a variety of mechanisms including effects on glycolysis. However, the understanding of how CR affects the response to cancer therapy is still rudimentary. Here, using the E mu-Myc transgenic mouse model of B-cell lymphoma, we report that by reducing protein translation, CR can reduce expression of the prosurvival Bcl-2 family member Mcl-1 and sensitize lymphomas to ABT-737-induced death in vivo. By using E mu-Myc lymphoma cells lacking p53, we showed that CR mimetics such as 2-deoxyglucose led to a decrease in Mcl-1 expression and sensitized lymphoma cells to ABT-737-induced death independently of p53. In keeping with this, E mu-Myc lymphoma cells lacking the BH3-only proapoptotic members Noxa, Puma, or Bim were also sensitized by CR mimetics to ABT-737-induced death. Remarkably, neither the loss of both Puma and Noxa, the loss of both Puma and Bim, nor the loss of all three BH3-only proteins prevented sensitization to ABT-737 induced by CR mimetics. Thus, CR can influence Mcl-1 expression and sensitize cells to BH3 mimetic-induced apoptosis, independently of the main BH3-only proteins and of p53. Exploiting this may improve the efficiency of, or prevent resistance to, cancer therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available