Treatment with Drugs Able to Reduce Iodine Efflux Significantly Increases the Intracellular Retention Time in Thyroid Cancer Cells Stably Transfected with Sodium Iodide Symporter Complementary Deoxyribonucleic Acid

Elisei, Rossella; Vivaldi, A; Ciampi, Raffaele; Faviana, Pinuccia; Basolo, Fulvio; Santini, Ferruccio; Traino, Claudio; Pacini, Furio; Pinchera, Aldo

doi:10.1210/jc.2005-2480

Cited by 40 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Compounds such as retinoic acid [20], valproic acid [21], and LY294002 [22] may induce increases in cellular iodide accumulation by enhancing NIS gene expressions via a variety of mechanisms. Chemicals that may reduce the efflux rates of iodine, such as lithium [23], DIDS, and tanespimycin [9,10] have also been recognized; however, the mechanisms relevant to such activities have not yet characterized in detail. Tanespimycin, a less liver toxic and more stable geldanamycin derivative [24] has been previously identified as a chemotherapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

“…Several investigation describing increased radioiodine accumulation in thyroid cells and thyroid cancer cells as the result of tanespimycin treatment were reported [9,10], but the specific mechanism relevant to this effect has yet to be characterized in detail. In this study, increased iodide uptake due to tanespimycin treatment was noted in FRTL-5 rat thyroid cancer and human NIS-expressing hNIS-ARO human thyroid cancer cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, tanespimycin-previously referred to as 17-AAG (17-allylamino-17-demethoxygeldanamycin)-is considered to be one of the promising agents. In addition to its marked anticancer effects, several investigators have noted previously that tanespimycin increases iodide accumulation in rat thyroid cells (PC-Cl3, FRTL-5) [9,10]. However, tanespimycin induces a slight reduction in NIS gene expression in PC-Cl3 cells, and it is generally assumed that the upregulation of NIS gene expression is not the mechanism by which tanespimycin acts.…”

mentioning

confidence: 99%

“…However, tanespimycin induces a slight reduction in NIS gene expression in PC-Cl3 cells, and it is generally assumed that the upregulation of NIS gene expression is not the mechanism by which tanespimycin acts. Tanespimycin has also been shown to reduce the rate of iodine efflux from hNIS-FRO, PC-Cl3, and FRTL-5 cells [9,10]. However, the actual mechanism of tanespimycin in cells has yet to be clearly elucidated.…”

mentioning

confidence: 99%

See 3 more Smart Citations

The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells

Youn

Song

et al. 2012

Nucl Med Mol Imaging

View full text Add to dashboard Cite

Purpose The heat shock protein 90 inhibitor, tanespimycin, is an anticancer agent known to increase iodine accumulation in normal and cancerous thyroid cells. Iodine accumulation is regulated by membrane proteins such as sodium iodide symporter (NIS) and pendrin (PDS), and thus we attempted to characterize the effects of tanespimycin on those genes. Methods Cells were incubated with tanespimycin in order to evaluate 125 I accumulation and efflux ability. Radioiodine uptake and efflux were measured by a gamma counter and normalized by protein amount. RT-PCR were performed to measure the level of gene expression. Results After tanespimycin treatment, 125 I uptake was increased by ∼2.5-fold in FRTL-5, hNIS-ARO, and hNIS-MDA-MB-231 cells, but no changes were detected in the hNIS-HeLa cells. Tanespimycin significantly reduced the radioiodine efflux rate only in the FRTL-5 cells. In the FRTL-5 and hNIS-ARO cells, PDS mRNA levels were markedly reduced; the only other observed alteration in the levels of NIS mRNA after tanespimycin treatment was an observed increase in the hNIS-ARO cells. Conclusions These results indicate that cellular responses against tanespimycin treatment differed between the normal rat thyroid cells and human cancer cells, and the reduction in the 125 I efflux rate by tanespimycin in the normal rat thyroid cells might be attributable to reduced PDS gene expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells

Youn

Song

et al. 2012

Nucl Med Mol Imaging

View full text Add to dashboard Cite

show abstract

“…This was based on the principle that TPO catalyzes iodination of proteins and promotes iodide retention within thyroid tissue. Trans-fection of NSCLC cells with both human NIS and TPO genes resulted in an increase in radioiodide uptake and retention and enhanced tumour cell apoptosis compared to isolated NIS gene delivery [173]. In contrast, Boland et al (2002) did not obtain a significant increase in the iodide retention time in SiHa human cervix tumour cells, even though the production of an enzymatically active TPO was tested and a significant increase in iodide organification was observed in the targeted cells [174].…”

Section: Prolongation Of Iodide Retention During Nis Gene Therapymentioning

confidence: 91%

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

Hingorani¹

2010

CCDT

View full text Add to dashboard Cite

The sodium iodide symporter (NIS) is responsible for thyroidal, salivary, gastric, intestinal and mammary iodide uptake. It was first cloned from the rat in 1996 and shortly thereafter from human and mouse tissue. In the intervening years, we have learned a great deal about the biology of NIS. Detailed knowledge of its genomic structure, transcriptional and post-transcriptional regulation and pharmacological modulation has underpinned the selection of NIS as an exciting approach for targeted gene delivery. A number of in vitro and in vivo studies have demonstrated the potential of using NIS gene therapy as a means of delivering highly conformal radiation doses selectively to tumours. This strategy is particularly attractive because it can be used with both diagnostic ( 99m Tc, 125 I, 124 I) and therapeutic ( 131 I, 186 Re, 188 Re, 211 At) radioisotopes and it lends itself to incorporation with standard treatment modalities, such as radiotherapy or chemoradiotherapy. In this article, we review the biology of NIS and discuss its development for gene therapy.

show abstract

Enhanced Iodide Sequestration by 3‐Biphenyl‐5,6‐dihydroimidazo[2,1‐b]thiazole in Sodium/Iodide Symporter (NIS)‐Expressing Cells

Lecat-Guillet

Ambroise

2008

ChemMedChem

View full text Add to dashboard Cite

The ability of the sodium/iodide symporter (NIS) to take up iodide has long provided the basis for cytoreductive gene therapy and cancer treatment with radioiodide. One of the major limitations of this approach is that radioiodide retention in NIS-expressing cells is not sufficient for their destruction. We identified and characterized a small organic molecule capable of increasing iodide retention in HEK293 cells permanently transfected with human NIS cDNA (hNIS-HEK293) and in the rat thyroid-derived cell line FRTL-5. In the presence of 3-biphenyl-4'-yl-5,6-dihydroimidazo[2,1-b]thiazole (ISA1), the transmembrane iodide concentration gradient was increased up to 4.5-fold. Our experiments indicate that the imidazothiazole derivative acts either by inhibiting anion efflux mechanisms, or by promoting the relocation of iodide into subcellular compartments. This new compound is not only an attractive chemical tool to investigate the mechanisms of iodide flux at the cellular level, but also opens promising perspectives in the treatment of cancer after NIS gene transfer.

show abstract

Treatment with Drugs Able to Reduce Iodine Efflux Significantly Increases the Intracellular Retention Time in Thyroid Cancer Cells Stably Transfected with Sodium Iodide Symporter Complementary Deoxyribonucleic Acid

Cited by 40 publications

References 30 publications

The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells

The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

Enhanced Iodide Sequestration by 3‐Biphenyl‐5,6‐dihydroimidazo[2,1‐b]thiazole in Sodium/Iodide Symporter (NIS)‐Expressing Cells

Contact Info

Product

Resources

About