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Cancers (Basel). 2020 Dec 07;12(12). doi: 10.3390/cancers12123675.

Autophagy in Osteosarcoma Cancer Stem Cells Is  Critical Process which Can Be Targeted by the Antipsychotic Drug Thioridazine.

Cancers

Olivier Camuzard, Marie-Charlotte Trojani, Sabine Santucci-Darmanin, Sophie Pagnotta, Véronique Breuil, Georges F Carle, Valérie Pierrefite-Carle

Affiliations

  1. Faculté de Médecine Nice, Université Côte d'Azur, UMR E-4320 TIRO-MATOs CEA/DRF/Institut Joliot, CEDEX 2, 06107 Nice, France.
  2. Service de Chirurgie Réparatrice et de la Main, CHU de Nice, 06001 Nice cedex 1, France.
  3. Service de Rhumatologie, CHU de Nice, 06001 Nice, France.
  4. Centre Commun de Microscopie Appliquée, Université Côte d'Azur, 06107 Nice, France.

PMID: 33297525 PMCID: PMC7762415 DOI: 10.3390/cancers12123675

Abstract

Cancer stem cells (CSCs) represent a minor population of cancer cells with stem cell-like properties which are able to fuel tumor growth and resist conventional treatments. Autophagy has been described to be upregulated in some CSCs and to play a crucial role by maintaining stem features and promoting resistance to both hostile microenvironments and treatments. Osteosarcoma (OS) is an aggressive bone cancer which mainly affects children and adolescents and autophagy in OS CSCs has been poorly studied. However, this is a very interesting case because autophagy is often deregulated in this cancer. In the present work, we used two OS cell lines showing different autophagy capacities to isolate CSC-enriched populations and to analyze the autophagy in basal and nutrient-deprived conditions. Our results indicate that autophagy is more efficient in CSCs populations compared to the parental cell lines, suggesting that autophagy is a critical process in OS CSCs. We also showed that the antipsychotic drug thioridazine is able to stimulate, and then impair autophagy in both CSC-enriched populations, leading to autosis, a cell death mediated by the Na+/K

Keywords: Na+/K+ ATPase; autophagy; autosis; cancer stem cells; osteosarcoma

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