Autophagy in Osteosarcoma Cancer Stem Cells Is Critical Process which Can Be Targeted by the Antipsychotic Drug Thioridazine
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 promoti...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/12/3675 |
| _version_ | 1797545426386157568 |
|---|---|
| author | Olivier Camuzard Marie-Charlotte Trojani Sabine Santucci-Darmanin Sophie Pagnotta Véronique Breuil Georges F. Carle Valérie Pierrefite-Carle |
| author_facet | Olivier Camuzard Marie-Charlotte Trojani Sabine Santucci-Darmanin Sophie Pagnotta Véronique Breuil Georges F. Carle Valérie Pierrefite-Carle |
| author_sort | Olivier Camuzard |
| collection | DOAJ |
| description | 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<sup>+</sup> ATPase pump and triggered by dysregulated accumulation of autophagosomes. Taken together, our results indicate that autophagy is very active in OS CSCs and that targeting this pathway to switch their fate from survival to death could provide a novel strategy to eradicate these cells in osteosarcoma. |
| first_indexed | 2024-03-10T14:15:15Z |
| format | Article |
| id | doaj.art-151588f5ae7c45cf9c4c592e43881735 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T14:15:15Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-151588f5ae7c45cf9c4c592e438817352023-11-20T23:47:45ZengMDPI AGCancers2072-66942020-12-011212367510.3390/cancers12123675Autophagy in Osteosarcoma Cancer Stem Cells Is Critical Process which Can Be Targeted by the Antipsychotic Drug ThioridazineOlivier Camuzard0Marie-Charlotte Trojani1Sabine Santucci-Darmanin2Sophie Pagnotta3Véronique Breuil4Georges F. Carle5Valérie Pierrefite-Carle6Faculté de Médecine Nice, Université Côte d’Azur, UMR E-4320 TIRO-MATOs CEA/DRF/Institut Joliot, CEDEX 2, 06107 Nice, FranceFaculté de Médecine Nice, Université Côte d’Azur, UMR E-4320 TIRO-MATOs CEA/DRF/Institut Joliot, CEDEX 2, 06107 Nice, FranceFaculté de Médecine Nice, Université Côte d’Azur, UMR E-4320 TIRO-MATOs CEA/DRF/Institut Joliot, CEDEX 2, 06107 Nice, FranceCentre Commun de Microscopie Appliquée, Université Côte d’Azur, 06107 Nice, FranceFaculté de Médecine Nice, Université Côte d’Azur, UMR E-4320 TIRO-MATOs CEA/DRF/Institut Joliot, CEDEX 2, 06107 Nice, FranceFaculté de Médecine Nice, Université Côte d’Azur, UMR E-4320 TIRO-MATOs CEA/DRF/Institut Joliot, CEDEX 2, 06107 Nice, FranceFaculté de Médecine Nice, Université Côte d’Azur, UMR E-4320 TIRO-MATOs CEA/DRF/Institut Joliot, CEDEX 2, 06107 Nice, FranceCancer 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<sup>+</sup> ATPase pump and triggered by dysregulated accumulation of autophagosomes. Taken together, our results indicate that autophagy is very active in OS CSCs and that targeting this pathway to switch their fate from survival to death could provide a novel strategy to eradicate these cells in osteosarcoma.https://www.mdpi.com/2072-6694/12/12/3675autophagyosteosarcomacancer stem cellsNa+/K+ ATPaseautosis |
| spellingShingle | Olivier Camuzard Marie-Charlotte Trojani Sabine Santucci-Darmanin Sophie Pagnotta Véronique Breuil Georges F. Carle Valérie Pierrefite-Carle Autophagy in Osteosarcoma Cancer Stem Cells Is Critical Process which Can Be Targeted by the Antipsychotic Drug Thioridazine Cancers autophagy osteosarcoma cancer stem cells Na+/K+ ATPase autosis |
| title | Autophagy in Osteosarcoma Cancer Stem Cells Is Critical Process which Can Be Targeted by the Antipsychotic Drug Thioridazine |
| title_full | Autophagy in Osteosarcoma Cancer Stem Cells Is Critical Process which Can Be Targeted by the Antipsychotic Drug Thioridazine |
| title_fullStr | Autophagy in Osteosarcoma Cancer Stem Cells Is Critical Process which Can Be Targeted by the Antipsychotic Drug Thioridazine |
| title_full_unstemmed | Autophagy in Osteosarcoma Cancer Stem Cells Is Critical Process which Can Be Targeted by the Antipsychotic Drug Thioridazine |
| title_short | Autophagy in Osteosarcoma Cancer Stem Cells Is Critical Process which Can Be Targeted by the Antipsychotic Drug Thioridazine |
| title_sort | autophagy in osteosarcoma cancer stem cells is critical process which can be targeted by the antipsychotic drug thioridazine |
| topic | autophagy osteosarcoma cancer stem cells Na+/K+ ATPase autosis |
| url | https://www.mdpi.com/2072-6694/12/12/3675 |
| work_keys_str_mv | AT oliviercamuzard autophagyinosteosarcomacancerstemcellsiscriticalprocesswhichcanbetargetedbytheantipsychoticdrugthioridazine AT mariecharlottetrojani autophagyinosteosarcomacancerstemcellsiscriticalprocesswhichcanbetargetedbytheantipsychoticdrugthioridazine AT sabinesantuccidarmanin autophagyinosteosarcomacancerstemcellsiscriticalprocesswhichcanbetargetedbytheantipsychoticdrugthioridazine AT sophiepagnotta autophagyinosteosarcomacancerstemcellsiscriticalprocesswhichcanbetargetedbytheantipsychoticdrugthioridazine AT veroniquebreuil autophagyinosteosarcomacancerstemcellsiscriticalprocesswhichcanbetargetedbytheantipsychoticdrugthioridazine AT georgesfcarle autophagyinosteosarcomacancerstemcellsiscriticalprocesswhichcanbetargetedbytheantipsychoticdrugthioridazine AT valeriepierrefitecarle autophagyinosteosarcomacancerstemcellsiscriticalprocesswhichcanbetargetedbytheantipsychoticdrugthioridazine |