ReferenceID 3419
The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells
J Neurosci
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. He
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- Reference Id
- 3419
- Evidence Id
- 20009
- Core Evidence Id
- 20009
- Source Reference Id
- 145
- Herb2 Reference Id
- HBREF000318
- Subject Paper Key
- HBIN037934_28292827
- Pubmed Id
- 28292827
- Doi
- 10.1523/JNEUROSCI.2296-16.2017
- Paper Title
- The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells
- Paper Abstract
- 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.SIGNIFICANCE STATEMENT In this work, we paved the road for a new therapeutic approach for the treatment of brain tumors, demonstrating the potential of using the cardioactive glycoside oleandrin as a coadjuvant drug to standard chemotherapeutics such as temozolomide. In murine models of glioma, we demonstrated that oleandrin significantly increased mouse survival and reduced tumor growth both directly on tumor cells and indirectly by promoting an antitumor brain microenvironment with a key protective role played by the neurotrophin brain-derived neurotrophic factor.
- Journal
- J Neurosci
- Publish Year
- 2017
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells
- Bilingual Status
- semi_complete