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

Abstract

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.

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer

“…The most investigated have been leukaemia [ 20 – 24 ], colon cancer [ 25 – 32 ], melanoma [ 33 – 37 ], pancreatic cancer [ 14 , 31 , 38 ] and prostate cancer [ 39 – 41 ]. Similar results have been described for the treatment of non-small-cell lung cancer (NSCLC) [ 16 ], breast cancer [ 31 , 42 ], ovarian cancer [ 31 , 43 , 44 ], hepatocellular carcinoma [ 45 , 46 ], malignant mesothelioma [ 47 , 48 ], thyroid cancer [ 49 , 50 ], oral squamous cell carcinoma [ 51 ], neuroblastoma [ 52 ] and glioma, including the difficult-to-treat glioblastoma multiform (GBM) [ 16 , 53 , 54 ].…”

Synthesis and Photophysical Properties of Fluorescent 6-Aryl-D-π-A Coumarin Derivatives

“…Then, cell viability was determined after 24 h at 37 °C by the MTT method. 23 As shown in Figure 8 , both coumarins have proved to be noncytotoxic against cell monolayers (CC50 = >100 μM). In parallel, the Nthy-ori 3–1 cells were incubated with 4c , 4e , and 4f (1.0 μM) for bioimaging studies and then analyzed by an epifluorescence microscope using blue (excitation 470–495 nm; emission 510–550 nm) and orange filters (excitation 530–550 nm; emission 575 nm).…”

“…Cultured cells were treated with different concentrations (10–100 μM) of 4c , 4e , and 4f . Then, cell viability was determined after 24 h at 37 °C by the MTT method . As shown in Figure , both coumarins have proved to be noncytotoxic against cell monolayers (CC50 = >100 μM).…”

The Variable Nature of Vitamin C—Does It Help When Dealing with Coronavirus?

“…Elevated free-radical levels can lead to the depletion of antioxidant mechanisms and the death of cancer cells. Apoptosis of breast cancer cells induced by AA at physiological concentrations (100 µM) was observed by Hong et al [ 117 ], while Tronci et al [ 118 ] demonstrated the antitumor effect of VC against papillary thyroid carcinoma cells. The oral intake of VC by patients with malignant tumors likely has no impact because, at lower concentrations, VC exhibits antioxidant, rather than pro-oxidant, activity [ 119 ].…”