Journal
NEUROSCIENCE LETTERS
Volume 513, Issue 1, Pages 106-110Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2012.02.022
Keywords
MDM2; TP53; Medulloblastoma; Apoptosis
Categories
Funding
- Alex's Lemonade Stand Foundation for Childhood Cancer
- Concern Foundation
Ask authors/readers for more resources
A critical component of the cellular stress response, the p53 tumor suppressor protein must be functional for many cancer therapies to be effective. Adjuvant therapies that augment p53 function are predicted to sensitize tumor cells to cancer therapies that rely upon p53 for their efficacy. Of those strategies currently being explored to enhance p53 function, inhibition of the ubiquitin ligase, MDM2, a negative regulator of p53, has shown promise. Here, we investigated whether MDM2 antagonism might be effective in inducing cell death in human medulloblastoma (MB) cells. Nutlin-3, a small-molecule inhibitor of MDM2, potently induced apoptosis in MB cells with wild-type TP53. Moreover, nutlin-3 potentiated p53 activation and growth impairment of MB cells in combination with the classic DNA-damaging agent doxorubicin. Together, these results support the concept that MDM2 antagonists may be therapeutically beneficial for patients with MB tumors. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
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