Abstract
Thyroid cancer is the most common malignant tumor of the endocrine system and the incidence has been increasing in recent years. In a great part of the differentiated carcinomas, thyrocytes are capable of uptaking iodide. In these cases, the main therapeutic approach includes thyroidectomy followed by ablative therapy with radioiodine. However, in part of the patients, the capacity to concentrate iodide is lost due to down-regulation of the sodium-iodide symporter (NIS), the protein responsible for transporting iodide into the thyrocytes. Thus, therapy with radioiodide becomes ineffective, limiting therapeutic options and reducing the life expectancy of the patient. Excessive ingestion of some flavonoids has been associated with thyroid dysfunction and goiter. Nevertheless, studies have shown that some flavonoids can be beneficial for thyroid cancer, by reducing cell proliferation and increasing cell death, besides increasing NIS mRNA levels and iodide uptake. Recent data show that the flavonoids apingenin and rutin are capable of increasing NIS function and expression in vivo. Herein we review literature data regarding the effect of flavonoids on thyroid cancer, besides the effect of these compounds on the expression and function of the sodium-iodide symporter. We will also discuss the possibility of using flavonoids as adjuvants for therapy of thyroid cancer.
Highlights
Flavonoid is the name of a great group of phytochemical compounds of natural origin, composed by aromatic substances widely distributed in the vegetable kingdom
Flavonoids were shown to have antiproliferative and cell re-differentiation effects, inducing the re-expression of NIS mRNA in an anaplastic thyroid carcinoma cell line (FRO), suggesting that these compounds could be important as therapeutic agents in the treatment of thyroid cancer [100,101,102]
The same research group demonstrated that in vitro treatment with quercetin for 48 h was able to decrease the expression of proteins that are essential for thyroid hormone synthesis: thyroglobulin, thyroperoxidase, thyrotropin receptor and sodium-iodide symporter, in addition to their respective mRNAs
Summary
Flavonoid is the name of a great group of phytochemical compounds of natural origin, composed by aromatic substances widely distributed in the vegetable kingdom. Even though the role of the flavonoids in human metabolism is not clear, the ingestion of these compounds is about 23 to 34 mg daily, and can reach two grams daily depending on eating habits, since they can be found in many types of food and beverages, including fruits, grains, salads, wine, teas, etc. Since 1958, it is known that flavonoids can affect thyroid function [7]. Recent data have suggested that flavonoids could have beneficial effects on thyroid cancer. Some flavonoids seem to increase iodide uptake in thyroid cell lines, such as myricetin [24] and apigenin [25], as well as in vivo thyroid iodide uptake [15]. Compounds able to increase iodide uptake in thyroid cancer could be useful as adjuvant in radioiodine therapy
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