Role of iodide metabolism in physiology and cancer

Abstract

Iodide (I) metabolism is crucial for the synthesis of thyroid hormones (THs) in the thyroid and the subsequent action of these hormones in the organism. I is principally transported by the sodium iodide symporter (NIS) and by the anion exchanger PENDRIN, and recent studies have demonstrated the direct participation of new transporters including anoctamin 1 (ANO1), cystic fibrosis transmembrane conductance regulator (CFTR) and sodium multivitamin transporter (SMVT). Several of these transporters have been found expressed in various tissues, implicating them in I recycling. New research supports the exciting idea that I participates as a protective antioxidant and can be oxidized to hypoiodite, a potent oxidant involved in the host defense against microorganisms. This was possibly the original role of I in biological systems, before the appearance of TH in evolution. I per se participates in its own regulation, and new evidence indicates that it may be antineoplastic, anti-proliferative and cytotoxic in human cancer. Alterations in the expression of I transporters are associated with tumor development in a cancer-type-dependent manner and, accordingly, NIS, CFTR and ANO1 have been proposed as tumor markers. Radioactive iodide has been the mainstay adjuvant treatment for thyroid cancer for the last seven decades by virtue of its active transport by NIS. The rapid advancement of techniques that detect radioisotopes, in particular I, has made NIS a preferred target-specific theranostic agent.

Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?

“…In the gastrointestinal tract, iodine uptake is mediated by intracellular iodine concentrations. Besides NIS, in the gut, it can be additionally absorbed via sodium multivitamin transporter (SMVT) and cystic fibrosis transporter (CFTR); however, only to small extents [4,55,56]. In inflammatory bowel disease (IBD), a reduction in the diversity of gut microbiota and a lower abundance of Firmicutes and Bacteroidetes have been observed.…”

“…Of note, iodide is not only suggested to be an antioxidant, but also antineoplastic, anti-proliferative, and cytotoxic in human cancer. Thus, alterations of iodide expression may be associated with tumor development in a cancer-type-dependent manner [56].…”

Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS)

“…Ican also be oxidized to OIwhich behaves similarly to OSCN - [91]. The LPO system has also been identified in mammary, lacrimal, and salivary glands, and a similar peroxidase, DUOX2, has been reported in the ovary, fallopian tube, and uterus, suggesting NIS in these tissues may be involved in maintaining sterility [5,[92][93][94]. NIS is also expressed in the epithelium of the choroid plexus where it has been shown to transport I -, SCN -, TcO 4 -, and Brout of the brain ventricle and into blood [95,96].…”

Iodine in abiotic and biotic environments

“…Thyroid hormones are also involved in tissue regeneration, maturation and functional activity of organs and organ systems [7,9,27,93], and oxygen-transport function of the blood [76,80]. Being an integral part of thyroid hormones, iodine is necessary for normal activity of the central nervous system, cardiovascular system, musculoskeletal system, as well as for the re- productive, digestive, hematopoietic and immune systems [12,27,28,64,84]. Iodine has some functions in the human body that are not mediated by its participation in the synthesis of thyroid hormones.…”

“…At the same time, the oxidation of I − to hypo-iodite (IO − ) makes it a potent oxidant with strong bactericidal activity. Iodine can also act as anti-inflammatory, antiproliferative and cytotoxic agent and has a protective effect against several types of cancer [28,87].…”