The glycoside oleandrin reduces glioma growth with direct and indirect effects on tumor cells

Stefano Garofalo, Alfonso Grimaldi, Giuseppina Chece, Alessandra Porzia, Stefania Morrone, Fabrizio Mainiero, Giuseppina D’Alessandro, Vincenzo Esposito, Barbara Cortese, Silvia Di Angelantonio, Flavia Trettel, Cristina Limatola

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3926-3939
Number of pages14
JournalJournal of Neuroscience
Volume37
Issue number14
DOIs
Publication statusPublished - Apr 5 2017

Keywords

  • Apoptosis
  • BDNF
  • Glioma
  • In vivo
  • Invasion
  • Oleandrin

ASJC Scopus subject areas

  • Neuroscience(all)

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