The Cross-Talk between Polyphenols and the Target Enzymes Related to Oxidative Stress-Induced Thyroid Cancer

Abstract

The most serious hallmark step of carcinogenesis is oxidative stress, which induces cell DNA damage. Although in normal conditions ROS are important second messengers, in pathological conditions such as cancer, due to imbalanced redox enzyme expression, oxidative stress can occur. Recent studies with firmly established evidence suggest an interdependence between oxidative stress and thyroid cancer based on thyroid hormone synthesis. Indeed, a reduced antioxidant defense system might play a part in several steps of progression in thyroid cancer. Based on studies that have been conducted previously, future drug designs for targeting enzymatic ROS sources, as a single agent or in combination, have to be tested. Polyphenols represent the potential for modulating biological events in thyroid cancer, including antioxidative activity. Targeting enzymatic ROS sources, without affecting the physiological redox state, might be an important purpose. As regards the underlying chemopreventive mechanisms of natural compounds that have been discussed in other cancer models, the confirmation of the influence of polyphenols on thyroid cancer is inconclusive and rarely available. Therefore, there is a need for further scientific investigations into the features of the antioxidative effects of polyphenols on thyroid cancer. The current review illustrates the association between some polyphenols and the key enzymes that take place in oxidation reactions in developing thyroid cancer cells. This review gives the main points of the enzymatic ROS sources act and redox signaling in normal physiological or pathological contexts and supplies a survey of the currently available modulators of TPO, LOX, NOX, DUOX, Nrf2, and LPO derived from polyphenols.

The protective role of nutritional antioxidants against oxidative stress in thyroid disorders

“…A significant difference in GPx activity and MDA levels was seen between the thyroid cancer patients before and after thyroidectomy in a study examining the change in OxS markers. Although thyroidectomy dramatically improved the oxidative status in favour of antioxidants, lipid peroxidation levels remained much more significant than in healthy thyroid people (25,121,124). Also, PTC patients exhibit a worse oxidative profile than patients with autoimmune thyroid disease and higher oxidative process rates than healthy individuals (125).…”

“…According to an analysis of the redox balance, sera antioxidant levels were lower in thyroid cancer patients than in healthy controls, and OxS marker sera levels in thyroid cancer patients were significantly higher than in the control samples ( 119 ). In addition, high concentrations of MDA in blood were detected in thyroid cancer patients, which unequivocally indicated reduced blood antioxidative capacity ( 120 , 121 ).…”

Therapeutic Potential of Polyphenols and Other Micronutrients of Marine Origin

“…This can lead to the inhibition of cancer cell growth and the induction of cell death. Marine polyphenols can also regulate the expression of genes involved in inflammation, such as cytokines and chemokines, thereby reducing inflammation [ 195 ].…”

“…For example, marine polyphenols can activate or inhibit enzymes, such as kinases and phosphatases, involved in signal transduction pathways, leading to altered cellular responses. Marine polyphenols can also regulate the expression of transcription factors, such as nuclear factor-kappa B (NF-κB), which plays a critical role in inflammation and immune responses [ 195 , 198 ].…”

Antioxidant Defense Capacity Is Reduced in Thyroid Stem/Precursor Cells Compared to Differentiated Thyrocytes

“…Oxidative stress is a risk factor for thyroid cancer [20,26,27], and it correlates with more aggressive features because ROS may repress genes involved in thyroid differentiation [28]. The antioxidant protection system of undifferentiated thyroid stem cells may therefore be important to preserve their normal biology, regulating the balance between stemness maintenance and the activation of self-renewal and differentiation [29][30][31][32].…”