Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines
High-dose of vitamin C (L-ascorbic acid, ascorbate) exhibits anti-tumoral effects, primarily mediated by pro-oxidant mechanisms. This cytotoxic effect is thought to affect the reciprocal crosstalk between redox balance and cell metabolism in different cancer types. Vitamin C also inhibits the growth...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/5/809 |
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| author | Laura Tronci Gabriele Serreli Cristina Piras Daniela Virginia Frau Tinuccia Dettori Monica Deiana Federica Murgia Maria Laura Santoru Martina Spada Vera Piera Leoni Julian Leether Griffin Roberta Vanni Luigi Atzori Paola Caria |
| author_facet | Laura Tronci Gabriele Serreli Cristina Piras Daniela Virginia Frau Tinuccia Dettori Monica Deiana Federica Murgia Maria Laura Santoru Martina Spada Vera Piera Leoni Julian Leether Griffin Roberta Vanni Luigi Atzori Paola Caria |
| author_sort | Laura Tronci |
| collection | DOAJ |
| description | High-dose of vitamin C (L-ascorbic acid, ascorbate) exhibits anti-tumoral effects, primarily mediated by pro-oxidant mechanisms. This cytotoxic effect is thought to affect the reciprocal crosstalk between redox balance and cell metabolism in different cancer types. Vitamin C also inhibits the growth of papillary thyroid carcinoma (PTC) cells, although the metabolic and redox effects remain to be fully understood. To shed light on these aspects, PTC-derived cell lines harboring the most common genetic alterations characterizing this tumor were used. Cell viability, apoptosis, and the metabolome were explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, and UHPLC/MS. Changes were observed in redox homeostasis, with increased reactive oxygen species (ROS) level and perturbation in antioxidants and electron carriers, leading to cell death by both apoptosis and necrosis. The oxidative stress contributed to the metabolic alterations in both glycolysis and TCA cycle. Our results confirm the pro-oxidant effect of vitamin C as relevant in triggering the cytotoxicity in PTC cells and suggest that inhibition of glycolysis and alteration of TCA cycle via NAD<sup>+</sup> depletion can play an important role in this mechanism of PTC cancer cell death. |
| first_indexed | 2024-03-10T11:15:09Z |
| format | Article |
| id | doaj.art-5dcaf6949ebb4f49af3c217b3d9cf59a |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T11:15:09Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-5dcaf6949ebb4f49af3c217b3d9cf59a2023-11-21T20:30:59ZengMDPI AGAntioxidants2076-39212021-05-0110580910.3390/antiox10050809Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell LinesLaura Tronci0Gabriele Serreli1Cristina Piras2Daniela Virginia Frau3Tinuccia Dettori4Monica Deiana5Federica Murgia6Maria Laura Santoru7Martina Spada8Vera Piera Leoni9Julian Leether Griffin10Roberta Vanni11Luigi Atzori12Paola Caria13Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB1 9NL, UKDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyDepartment of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, ItalyHigh-dose of vitamin C (L-ascorbic acid, ascorbate) exhibits anti-tumoral effects, primarily mediated by pro-oxidant mechanisms. This cytotoxic effect is thought to affect the reciprocal crosstalk between redox balance and cell metabolism in different cancer types. Vitamin C also inhibits the growth of papillary thyroid carcinoma (PTC) cells, although the metabolic and redox effects remain to be fully understood. To shed light on these aspects, PTC-derived cell lines harboring the most common genetic alterations characterizing this tumor were used. Cell viability, apoptosis, and the metabolome were explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, and UHPLC/MS. Changes were observed in redox homeostasis, with increased reactive oxygen species (ROS) level and perturbation in antioxidants and electron carriers, leading to cell death by both apoptosis and necrosis. The oxidative stress contributed to the metabolic alterations in both glycolysis and TCA cycle. Our results confirm the pro-oxidant effect of vitamin C as relevant in triggering the cytotoxicity in PTC cells and suggest that inhibition of glycolysis and alteration of TCA cycle via NAD<sup>+</sup> depletion can play an important role in this mechanism of PTC cancer cell death.https://www.mdpi.com/2076-3921/10/5/809vitamin CPTC cellsROScell metabolismTCA cycleantioxidants |
| spellingShingle | Laura Tronci Gabriele Serreli Cristina Piras Daniela Virginia Frau Tinuccia Dettori Monica Deiana Federica Murgia Maria Laura Santoru Martina Spada Vera Piera Leoni Julian Leether Griffin Roberta Vanni Luigi Atzori Paola Caria Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines Antioxidants vitamin C PTC cells ROS cell metabolism TCA cycle antioxidants |
| title | Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines |
| title_full | Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines |
| title_fullStr | Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines |
| title_full_unstemmed | Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines |
| title_short | Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines |
| title_sort | vitamin c cytotoxicity and its effects in redox homeostasis and energetic metabolism in papillary thyroid carcinoma cell lines |
| topic | vitamin C PTC cells ROS cell metabolism TCA cycle antioxidants |
| url | https://www.mdpi.com/2076-3921/10/5/809 |
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