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Angeletti F, Fossati G, Pattarozzi A, et al. Inhibition of the Autophagy Pathway Synergistically Potentiates the Cytotoxic Activity of Givinostat (ITF2357) on Human Glioblastoma Cancer Stem Cells. Front Mol Neurosci. 2016;9:107doi: 10.3389/fnmol.2016.00107.
Angeletti, F., Fossati, G., Pattarozzi, A., Würth, R., Solari, A., Daga, A., Masiello, I., Barbieri, F., Florio, T., & Comincini, S. (2016). Inhibition of the Autophagy Pathway Synergistically Potentiates the Cytotoxic Activity of Givinostat (ITF2357) on Human Glioblastoma Cancer Stem Cells. Frontiers in molecular neuroscience, 9107. https://doi.org/10.3389/fnmol.2016.00107
Angeletti, Francesca, et al. "Inhibition of the Autophagy Pathway Synergistically Potentiates the Cytotoxic Activity of Givinostat (ITF2357) on Human Glioblastoma Cancer Stem Cells." Frontiers in molecular neuroscience vol. 9 (2016): 107. doi: https://doi.org/10.3389/fnmol.2016.00107
Angeletti F, Fossati G, Pattarozzi A, Würth R, Solari A, Daga A, Masiello I, Barbieri F, Florio T, Comincini S. Inhibition of the Autophagy Pathway Synergistically Potentiates the Cytotoxic Activity of Givinostat (ITF2357) on Human Glioblastoma Cancer Stem Cells. Front Mol Neurosci. 2016 Oct 27;9:107. doi: 10.3389/fnmol.2016.00107. eCollection 2016. PMID: 27833530; PMCID: PMC5081386.
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Front Mol Neurosci. 2016 Oct 27;9:107. doi: 10.3389/fnmol.2016.00107. eCollection 2016.

Inhibition of the Autophagy Pathway Synergistically Potentiates the Cytotoxic Activity of Givinostat (ITF2357) on Human Glioblastoma Cancer Stem Cells.

Frontiers in molecular neuroscience

Francesca Angeletti, Gianluca Fossati, Alessandra Pattarozzi, Roberto Würth, Agnese Solari, Antonio Daga, Irene Masiello, Federica Barbieri, Tullio Florio, Sergio Comincini

Affiliations

  1. Department of Biology and Biotechnology, University of Pavia Pavia, Italy.
  2. Preclinical Research Department Italfarmaco Research Center, Italfarmaco S.p.A Cinisello Balsamo, Italy.
  3. Department of Internal Medicine, Centre of Excellence for Biomedical Research, University of Genova Genova, Italy.
  4. Regenerative Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Genova, Italy.

PMID: 27833530 PMCID: PMC5081386 DOI: 10.3389/fnmol.2016.00107

Abstract

Increasing evidence highlighted the role of cancer stem cells (CSCs) in the development of tumor resistance to therapy, particularly in glioblastoma (GBM). Therefore, the development of new therapies, specifically directed against GBM CSCs, constitutes an important research avenue. Considering the extended range of cancer-related pathways modulated by histone acetylation/deacetylation processes, we studied the anti-proliferative and pro-apoptotic efficacy of givinostat (GVS), a pan-histone deacetylase inhibitor, on cell cultures enriched in CSCs, isolated from nine human GBMs. We report that GVS induced a significant reduction of viability and self-renewal ability in all GBM CSC cultures; conversely, GVS exposure did not cause a significant cytotoxic activity toward differentiated GBM cells and normal mesenchymal human stem cells. Analyzing the cellular and molecular mechanisms involved, we demonstrated that GVS affected CSC viability through the activation of programmed cell death pathways. In particular, a marked stimulation of macroautophagy was observed after GVS treatment. To understand the functional link between GVS treatment and autophagy activation, different genetic and pharmacological interfering strategies were used. We show that the up-regulation of the autophagy process, obtained by deprivation of growth factors, induced a reduction of CSC sensitivity to GVS, while the pharmacological inhibition of the autophagy pathway and the silencing of the key autophagy gene

Keywords: autophagy; cancer stem cell; glioblastoma multiforme; histone deacetylase inhibitor; programmed cell death

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