Abstract
Thyroid cancer cells demonstrate an increase in oxidative stress and decreased antioxidant action, but the effects of this increased oxidative stress on cell function remain unknown. We aimed to identify changes in the metabolism of thyroid cancer cells caused by oxidative stress, using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Samples of thyroid cancer and healthy thyroid tissue were collected from patients undergoing thyroidectomy and analyzed with 1H-NMR spectroscopy for a wide array of metabolites. We found a significant increase in lactate content in thyroid cancer tissue compared to healthy tissue. Metabolomic analysis demonstrated significant differences between cancer tissue and healthy tissue, including an increase in aromatic amino acids, and an average decrease in citrate in thyroid cancer tissue. We hypothesize that these changes in metabolism may be due to an oxidative stress-related decrease in activity of the Krebs cycle, and a shift towards glycolysis in cancer tissue. Thus, thyroid cancer cells are able to reprogram their metabolic activity to survive in conditions of high oxidative stress and with a compromised antioxidant system. Our findings, for the first time, suggested a connection between oxidative stress and the alteration of the metabolic profile in thyroid tumors.
Highlights
The overproduction of free radicals, and consequent increase in oxidative stress, leads to irreversible cell damage, which is associated with cardiovascular and chronic diseases, and with cancer [1,2,3,4,5]
Spectroscopy in order to clarify the biochemical and metabolic changes that occur in thyroid cancer, and to evaluate their relationship with increased oxidative stress
High-resolution 1 H-Nuclear magnetic resonance (NMR) analyses of biopsy extracts have shown a variation in the molecular proportion of various metabolites relative to the total metabolite content between healthy and cancer tissues
Summary
The overproduction of free radicals, and consequent increase in oxidative stress, leads to irreversible cell damage, which is associated with cardiovascular and chronic diseases, and with cancer [1,2,3,4,5]. We used electronic paramagnetic resonance spectroscopy (EPR). We have shown in thyroid cancer a reduction of the expression of glutathione peroxidase (GPx1) and thioredoxin reductase (TrxR1), two seleno-enzymes with antioxidant action. TrxR1 is the only enzyme known to catalyze the reduction of thioredoxins—proteins, characterized by the presence of two cysteines, that act as antioxidants by reducing oxidized proteins through cysteine thiol-disulfide. Our data demonstrates the involvement of oxidative stress in thyroid tumors, consistent with previous literature, utilizing the novel method of EPR spectroscopy [9]. Compared to other methods of detecting oxidative stress, EPR spectroscopy allows us to obtain a direct measurement of the primary species, rather than its effect [10]. The downstream effects exerted by oxidative stress on the biochemical and metabolic pathways involved in thyroid cancer remain unknown.
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