Vitamin C Cytotoxicity and Its Effects in Redox Homeostasis and Energetic Metabolism in Papillary Thyroid Carcinoma Cell Lines.

Autor:	Tronci L; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Serreli G; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Piras C; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Frau DV; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Dettori T; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Deiana M; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Murgia F; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Santoru ML; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Spada M; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Leoni VP; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Griffin JL; Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB1 9NL, UK., Vanni R; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Atzori L; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy., Caria P; Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km 4.5, 09042 Monserrato, Italy.
Jazyk:	angličtina
Zdroj:	Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2021 May 20; Vol. 10 (5). Date of Electronic Publication: 2021 May 20.
DOI:	10.3390/antiox10050809
Abstrakt:	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 + depletion can play an important role in this mechanism of PTC cancer cell death.
Databáze:	MEDLINE
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