Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 14, Pages 3926-3939Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2296-16.2017
Keywords
apoptosis; BDNF; glioma; in vivo; invasion; oleandrin
Categories
Funding
- Associazione Italiana per la Ricerca sul Cancro [IG2015-16699]
- Associazione Italiana per la Ricerca sul Cancro [My First AIRC Grant (MFAG)] [16803]
Ask authors/readers for more resources
Oleandrin is a glycoside that inhibits the ubiquitous enzyme Na+/K+-ATPase. In addition to its known effects on cardiac muscle, recent in vitro and in vivo evidence highlighted its potential for anticancer properties. Here, we evaluated for the first time the effect of oleandrin on brain tumors. To this aim, mice were transplanted with human or murine glioma and analyzed for tumor progression upon oleandrin treatment. In both systems, oleandrin impaired glioma development, reduced tumor size, and inhibited cell proliferation. We demonstrated that oleandrin does the following: (1) enhances the brain-derived neurotrophic factor (BDNF) level in the brain; (2) reduces both microglia/macrophage infiltration and CD68 immunoreactivity in the tumor mass; (3) decreases astrogliosis in peritumoral area; and (4) reduces glioma cell infiltration in healthy parenchyma. In BDNF-deficient mice (bdnftm1Jae/J) and in glioma cells silenced for TrkB receptor expression, oleandrin was not effective, indicating a crucial role for BDNF in oleandrin's protective and antitumor functions. In addition, we found that oleandrin increases survival of temozolomide-treated mice. These results encourage the development of oleandrin as possible coadjuvant agent in clinical trials of glioma treatment.
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