A possible role for selenoprotein glutathione peroxidase (GPx1) and thioredoxin reductases (TrxR1) in thyroid cancer: our experience in thyroid surgery

Alessio Metere, Francesca Frezzotti, Claire Elizabeth Graves, Massimo Vergine, Alessandro De Luca, Donatella Pietraforte, Laura Giacomelli, Alessio Metere, Francesca Frezzotti, Claire Elizabeth Graves, Massimo Vergine, Alessandro De Luca, Donatella Pietraforte, Laura Giacomelli

Abstract

Background: Oxidative stress is responsible for some alterations in the chemical structure and, consequently, in the function of proteins, lipids, and DNA. Recent studies have linked oxidative stress to cancers, particularly thyroid cancer, but the mechanisms remain unclear. Here, we further characterize the role of oxidative stress in thyroid cancer by analyzing the expression of two selenium antioxidant molecules, glutathione peroxidase (GPx1) and thioredoxin reductase (TrxR1) in thyroid cancer cells.

Methods: Samples of both healthy thyroid tissue and thyroid tumor were taken for analysis after total thyroidectomy. The expression of GPx1 and TrxR1 was revealed by Western blot analysis and quantified by densitometric analyses, while the evaluation of free radicals was performed by Electron Paramagnetic Resonance (EPR)-spin trapping technique.

Results: Our results show a decrease in the expression of GPx1 and TrxR1 (- 45.7 and - 43.2% respectively, p < 0.01) in the thyroid cancer cells compared to the healthy cells. In addition, the EPR technique shows an increase of free radicals in tumor tissue, significantly higher than that found in healthy thyroid tissue (+ 116.3%, p < 0.01).

Conclusions: Our findings underscore the relationship between thyroid cancer and oxidative stress, showing the imbalance of the oxidant/antioxidant system in thyroid cancer tissue. These results suggest that either the inability to produce adequate antioxidant defense or an increased consumption of antioxidants, due to the hyper-production of free radicals, may play a crucial role in thyroid cancer.

Keywords: Glutathione peroxidase (GPx1); Oxidative stress; Selenium enzymes; Thioredoxin reductases (TrxR1); Thyroid cancer.

Figures

Fig. 1
Fig. 1
a Densitometric analysis of Western blotting reveals a meaningful decrease of the GPx expression (− 44.4 ± 2.8%, p < 0.01) in cancer (red line) with respect to the healthy thyroid tissue (black line). No differences were found between cancer and healthy tissue for the actin expression (data not shown). b Western blotting analysis of GPx1 and actin expression in cancer (C) and healthy (H) thyroid tissue. The numbers below identify the patient (see Table 1). NS not significant, *p < 0.01)
Fig. 2
Fig. 2
a Densitometric analysis of Western blotting shows also in this case a significant decrease of TrxR1 expression (− 49 ± 1.2%, p < 0.01) in cancer (red line) with respect to the healthy thyroid tissue (black line). b Western blotting analysis of TrxR1 and actin in cancer (C) and healthy (H) thyroid tissue shows a general reduction of TrxR1 in cancer (C). The numbers below identify the patient (see Table 1). NS not significant, *p < 0.01
Fig. 3
Fig. 3
EPR measurement of reactive oxygen species in thyroid tissue. The red line shows the concentration of CP· in cancer tissue (C), while the black line shows the concentration of CP· detected in healthy thyroid tissue (H). The statistical analysis was significant for all patients

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