Dexamethasone Stimulation of Retinoic Acid-Induced Sodium Iodide Symporter Expression and Cytotoxicity of 131-I in Breast Cancer Cells

Unterholzner, S.; Willhauck, Michael J.; Cengic, Neziha; Schütz, Martin; Göke, Burkhard; Morris, John C.; Spitzweg, Christine

doi:10.1210/jc.2005-0779

Cited by 47 publications

(43 citation statements)

References 55 publications

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“…A large number of agents with very different mechanisms of action have been utilized to stimulate NIS expression, such as redifferentiating agents [12,15,[33][34][35], or compounds that are reported to physiologically regulate NIS in breast cells [7,[36][37][38]. Retinoid acid, especially in the presence of other compounds such as dexamethasone, induce NIS and iodide uptake in breast cancer cells [12,15,[33][34][35] and in animal models [39]. Even though these findings suggest their potential clinical use, as yet no clinical trials have been presently designed to this aim and additional strategies can be foreseen.…”

Section: Discussionmentioning

confidence: 99%

“…In breast cancer cells, many authors reported that retinoic acid is a powerful enhancer of NIS expression especially in association with corticosteroids [12][13][14]. Furthermore, in one report it was also observed that retinoic acid and dexamethasone treatment determined a significant 131 I-induced cytotoxicity in breast cancer cells [15].…”

Section: Introductionmentioning

confidence: 97%

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The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

Fortunati

Catalano

Marano

et al. 2010

Breast Cancer Res Treat

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International audienceNew drugs with anti-tumor activity, also able to modify the expression of selected molecules, are under evaluation in breast cancer which is becoming resistant to conventional treatment, or in metastatic disease. The sodium-iodide symporter (NIS), which mediates iodide uptake into thyroid cells, and is the molecular basis of radioiodine imaging and therapy in thyroid cancer, is also expressed in a large portion of breast tumors. Since NIS expression in breast cancer is not sufficient for a significant iodide uptake, drugs able to induce its expression and correct function are under evaluation. In the present study, we report for the first time that the pan-deacetylase (DAC) inhibitor LBH589 (panobinostat) significantly induced NIS, both as mRNA and as protein, through the increase of NIS promoter activity, with the final consequence of obtaining a significant up-take of iodide in MCF7, T47D, and MDA-MB231 breast cancer cells. Moreover, we observed that LBH589 causes a significant reduction in cell viability of estrogen-sensitive and -insensitive breast cancer cells within nanomolar range. The anti-tumor effect of LBH589 is sustained by apoptosis induction and cell cycle arrest in G/M. In conclusion, our data suggest that LBH589 might be a powerful tool in the management of breast cancer due to its multiple effects and support a potential application of LBH589 in the diagnosis and treatment of this disease

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

Fortunati

Catalano

Marano

et al. 2010

Breast Cancer Res Treat

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“…Combined treatment with ATRA/dexamethasone in vivo was associated with significant 123 I accumulation in MCF-7 xenografts that, by ex vivo gamma counting, revealed a 3.3-fold increase in iodide accumulation as compared to control tumours treated with ATRA alone. NIS mRNA and protein expression were detectable in ATRA/Dex treated MCF-7 tumours by RT-PCR and immunohistochemistry, respectively [121]. These encouraging results have set the stage for further studies aiming to exploit the potential reporter and therapeutic functions of NIS in managing breast cancer.…”

Section: Pharmacological Modulation Of Extrathyroidal Nis Expressionmentioning

confidence: 75%

“…Therefore, strategies aimed at upregulating NIS expression should lead to superior cytotoxic effect, by virtue of exploitation of the above principle. The use of dexamethasone and retinoids to enhance endogenous NIS expression in breast cancer models has been previously discussed [119,121]. This strategy has also been investigated following exogenous NIS transfer in breast and prostate cancer models.…”

Section: Upregulation Of Nis Expressionmentioning

confidence: 99%

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

Hingorani¹

2010

CCDT

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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.

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“…In more recent studies, we and others have demonstrated that dexamethasone (Dex) is able to significantly enhance atRA-induced NIS expression and iodide accumulation in MCF-7 cells in vitro and in vivo [10,[13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of retinoic acid-induced functional sodium iodide symporter (NIS) expression and cytotoxicity of 131I by carbamazepine in breast cancer cells

Willhauck

O’Kane

Wunderlich

et al. 2010

Breast Cancer Res Treat

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Incubation with CBZ stimulated atRA-induced iodide accumulation up to 2-fold in a concentration-dependent manner, while atRA/Dex-stimulated iodide uptake was further stimulated up to 1.5-fold by additional CBZ treatment based on significantly increased NIS mRNA and protein levels. This stimulatory effect of CBZ was shown to be dependent on the PI3K-Akt pathway without involvement of mTOR. In contrast, treatment with CBZ alone had no effect on functional NIS expression. Moreover, selective cytotoxicity of 131 I was significantly increased from approximately 20 % in MCF-7 cells treated with atRA alone to 50% after treatment with CBZ in the presence of atRA, which was further enhanced to 90% after combined treatment with atRA/Dex/CBZ.In conclusion, CBZ represents another potent stimulator of atRA-induced functional NIS expression resulting in an enhanced selective killing effect of 131 I in MCF-7 breast cancer cells.3

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Dexamethasone Stimulation of Retinoic Acid-Induced Sodium Iodide Symporter Expression and Cytotoxicity of 131-I in Breast Cancer Cells

Abstract: Treatment with Dex in the presence of atRA significantly increases functional NIS expression levels in addition to inhibiting iodide efflux, resulting in an enhanced selective killing effect of 131-I in MCF-7 breast cancer cells.

Cited by 47 publications

References 55 publications

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

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

Stimulation of retinoic acid-induced functional sodium iodide symporter (NIS) expression and cytotoxicity of 131I by carbamazepine in breast cancer cells

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