The Flavonoid Quercetin Regulates Growth and Gene Expression in Rat FRTL-5 Thyroid Cells

Abstract

Quercetin is the most consumed flavonoid present in fruits and vegetables. There has been increased interest in the possible health benefits of quercetin and other flavonoids. Because it is reported that these compounds have some antithyroid properties, we were interested whether, and by what mechanism, quercetin might regulate thyroid cell growth and function. In this report we show that quercetin inhibits thyroid cell growth in association with inhibition of insulin-modulated phosphatidylinositol 3-kinase-Akt kinase activity. Furthermore, quercetin decreases TSH-modulated RNA levels of the thyroid-restricted gene sodium/iodide symporter (NIS). We associated down-regulation of NIS RNA levels with inhibition of iodide uptake at comparable quercetin concentrations and could show that the inhibitory effect of quercetin on NIS RNA levels and iodide uptake is reproduced by inhibitors of the phospholipase-A 2 /lipoxygenase pathway. The specific inhibitor of protein kinase A, H89, only partially inhibited TSH-increased NIS expression and did not reproduce the quercetin effect. The quercetin studies thus reveal that the phospholipase-A 2 /lipoxygenase pathway appears to play an important role in TSH regulation of NIS gene expression, whereas quercetin inhibition of growth appears to involve an effect on insulin/IGF-I-Akt signaling. The data raise the possibility that quercetin may be a novel disruptor of thyroid function, which has potential effects on, or use in, the therapy of thyroid diseases. (Endocrinology 149: 84 -92, 2008)

Phosphoinositide-3-kinase inhibition induces sodium/iodide symporter expression in rat thyroid cells and human papillary thyroid cancer cells

“…2-fold respectively; Fig. 4), consistent with the previous observations with LY294002 (Garcia & Santisteban 2002, Giuliani et al 2007. These data indicate that PI-103 induces the expression of Nis mRNA, but not iodide uptake.…”

“…The present study and some previous reports (Garcia & Santisteban 2002, Giuliani et al 2007) indicated that these PI3K inhibitors, including PI-103, significantly induced the Nis mRNA expression. PI-103 likely inhibits the translation and/or post-translational regulation of NIS.…”

“…Each inhibitor possibly has different 'off-target' effects, which may influence NIS expression at the different levels. A potent PI3K inhibitor, Quercetin, paradoxically reduces the Nis mRNA expression in FRTL-5 cells through inhibition of phospholipase-A 2 pathway (Giuliani et al 2007), although the NISinducing LY294002 is a derivative of Quercetin.…”

“…Phosphoinositide-3-kinase (PI3K) is one of the major mediators of insulin/IGF signaling. Selective inhibitors of PI3K, such as LY294002 and Wortmannin, significantly increase Nis mRNA expression in rat thyroid cells by stimulating its transcription (Garcia & Santisteban 2002, Giuliani et al 2007. Although enhancement of iodide uptake with LY294002 has been incidentally observed in TSH-stimulated FRTL-5 cells (Kogai et al 2008), the effects of PI3K inhibition on the iodide uptake in thyroid cells have not been well characterized.…”

Experimental studies and Development of Modelling equation of Quercetin from Pine apple peel using Soxhlet Extractor

“…These free radicals crop up biologically in the body [4] and have the ability to destroy cell membranes, aggravate the aging process, interrelate with inherent substances and also lead to a number of ailments such as heart disease [5] and cancer [6]. Hence, antioxidants [7] like quercetin are able to counteract the free radicals [8] and help in lessening and also preventing the damages caused by them. It has been found that quercetin has the potential to become an effective remedy for prevention and treatment of several disorders [9].…”