In vitro effects of ascorbic acid on viability and metabolism of patients’ osteosarcoma stem cells
Stagnation in novelties of osteosarcoma (OS) treatment indicates the need for new therapeutic methods. OS cancer stem cells (OS-CSC) are taught to have the ability to self-renew and develop mechanisms of anticancer drug resistance, and this is why it is difficult to eradicate them. Their metabolism...
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| Language: | English |
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2022-12-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2022-0040 |
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| author | Jovičić Marijana Šimić Pušić Maja Antunović Maja Ledinski Maja Librenjak Lucija Kolundžić Robert Ribičić Tomislav Trkulja Vladimir Urlić Inga |
| author_facet | Jovičić Marijana Šimić Pušić Maja Antunović Maja Ledinski Maja Librenjak Lucija Kolundžić Robert Ribičić Tomislav Trkulja Vladimir Urlić Inga |
| author_sort | Jovičić Marijana Šimić |
| collection | DOAJ |
| description | Stagnation in novelties of osteosarcoma (OS) treatment indicates the need for new therapeutic methods. OS cancer stem cells (OS-CSC) are taught to have the ability to self-renew and develop mechanisms of anticancer drug resistance, and this is why it is difficult to eradicate them. Their metabolism has been recognized as a potential target of therapeutic action. Ascorbic acid (AA) is considered to act pro-oxidative against OS-CSC in vitro by oxidative effect and by inhibition of glycolysis. This study examined an in vitro impact of AA on OS-CSC metabolism isolated from patients’ biopsies, with the aim of better understanding of OS-CSC metabolism and the action of AA on OS-CSC. OS-CSC were isolated using a sphere culture system and identified as stem cells using Hoechst 33342 exclusion assay. Determination of the dominant type of metabolism of OS-CSC, parental OS cells, human mesenchymal stem cells (hMSC) and U2OS OS lineage before and after AA treatment was done by Seahorse XF (Agilent). Cytotoxicity of high-dose AA was confirmed by the MTT test and was proven for all the examined cell types as well as HEK293. Seahorse technology showed that OS-CSC can potentially use both glycolysis and oxidative phosphorylation (OXPHOS), and can turn to glycolysis and slow metabolic potential in unfavorable conditions such as incubation in AA. |
| format | Article |
| id | doaj-art-b4649647c42d45fa89db900adee8103d |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-b4649647c42d45fa89db900adee8103d2025-02-02T23:44:34ZengSciendoActa Pharmaceutica1846-95582022-12-0172459961310.2478/acph-2022-0040In vitro effects of ascorbic acid on viability and metabolism of patients’ osteosarcoma stem cellsJovičić Marijana Šimić0Pušić Maja1Antunović Maja2Ledinski Maja3Librenjak Lucija4Kolundžić Robert5Ribičić Tomislav6Trkulja Vladimir7Urlić Inga8Children’s Hospital Zagreb, Department of Pediatric Orthopedics, Zagreb, CroatiaFaculty of Science, University of Zagreb Department of Molecular Biology, ZagrebCroatiaFaculty of Science, University of Zagreb Department of Molecular Biology, ZagrebCroatiaFaculty of Science, University of Zagreb Department of Molecular Biology, ZagrebCroatiaFaculty of Science, University of Zagreb Department of Molecular Biology, ZagrebCroatiaDepartment of Trauma Surgery University Hospital Centre “Sestre Milosrdnice”, Zagreb, CroatiaChildren’s Hospital Zagreb, Department of Pediatric Orthopedics, Zagreb, CroatiaSchool of Medicine, University of Zagreb, Department of Pharmacology Zagreb, CroatiaFaculty of Science, University of Zagreb Department of Molecular Biology, ZagrebCroatiaStagnation in novelties of osteosarcoma (OS) treatment indicates the need for new therapeutic methods. OS cancer stem cells (OS-CSC) are taught to have the ability to self-renew and develop mechanisms of anticancer drug resistance, and this is why it is difficult to eradicate them. Their metabolism has been recognized as a potential target of therapeutic action. Ascorbic acid (AA) is considered to act pro-oxidative against OS-CSC in vitro by oxidative effect and by inhibition of glycolysis. This study examined an in vitro impact of AA on OS-CSC metabolism isolated from patients’ biopsies, with the aim of better understanding of OS-CSC metabolism and the action of AA on OS-CSC. OS-CSC were isolated using a sphere culture system and identified as stem cells using Hoechst 33342 exclusion assay. Determination of the dominant type of metabolism of OS-CSC, parental OS cells, human mesenchymal stem cells (hMSC) and U2OS OS lineage before and after AA treatment was done by Seahorse XF (Agilent). Cytotoxicity of high-dose AA was confirmed by the MTT test and was proven for all the examined cell types as well as HEK293. Seahorse technology showed that OS-CSC can potentially use both glycolysis and oxidative phosphorylation (OXPHOS), and can turn to glycolysis and slow metabolic potential in unfavorable conditions such as incubation in AA.https://doi.org/10.2478/acph-2022-0040osteosarcomacancer stem cellstumor cell metabolismascorbic acid |
| spellingShingle | Jovičić Marijana Šimić Pušić Maja Antunović Maja Ledinski Maja Librenjak Lucija Kolundžić Robert Ribičić Tomislav Trkulja Vladimir Urlić Inga In vitro effects of ascorbic acid on viability and metabolism of patients’ osteosarcoma stem cells Acta Pharmaceutica osteosarcoma cancer stem cells tumor cell metabolism ascorbic acid |
| title | In vitro effects of ascorbic acid on viability and metabolism of patients’ osteosarcoma stem cells |
| title_full | In vitro effects of ascorbic acid on viability and metabolism of patients’ osteosarcoma stem cells |
| title_fullStr | In vitro effects of ascorbic acid on viability and metabolism of patients’ osteosarcoma stem cells |
| title_full_unstemmed | In vitro effects of ascorbic acid on viability and metabolism of patients’ osteosarcoma stem cells |
| title_short | In vitro effects of ascorbic acid on viability and metabolism of patients’ osteosarcoma stem cells |
| title_sort | in vitro effects of ascorbic acid on viability and metabolism of patients osteosarcoma stem cells |
| topic | osteosarcoma cancer stem cells tumor cell metabolism ascorbic acid |
| url | https://doi.org/10.2478/acph-2022-0040 |
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