Human thyroid cancer cells as a source of iso-genic, iso-phenotypic cell lines with or without functional p53

Zinc at concentrations of 150, microM or higher induced necrosis as well as apoptosis in thyroid cancer cell lines. Necrosis was induced by zinc in a dose-dependent manner, whereas apoptosis did not increase at higher concentrations of zinc. The expression of the antiapoptotic protein phosphorylated Bad was markedly increased, whereas the expression of the proapoptotic proteins Bax and Bad decreased following Zn(2+) exposure. Zn(2+) induced rapid degradation of IkappaB, and an increase in the binding of nuclear transcription factor-kappaB (NF-kappaB). These observations indicate that antiapoptotic pathways were activated in thyroid cancer cells following exposure to Zn(2+). This may be a self-defence mechanism against apoptosis and may underlie the general resistance of thyroid cancer cells to apoptotic stimuli. Zinc may be a potential cytotoxic agent for the treatment of thyroid cancer.

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FOXE1 regulates migration and invasion in thyroid cancer cells and targets ZEB1

Endocrine Related Cancer ◽

10.1530/erc-19-0156 ◽

2020 ◽

Vol 27 (3) ◽

pp. 137-151 ◽

Cited By ~ 2

Author(s):

Jesús Morillo-Bernal ◽

Lara P Fernández ◽

Pilar Santisteban

Keyword(s):

Cell Migration ◽

Thyroid Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Susceptibility ◽

Human Thyroid ◽

Migration And Invasion ◽

Migration Ability ◽

Mesenchymal Transition ◽

Thyroid Cancer Cells

FOXE1 is a thyroid-specific transcription factor essential for thyroid gland development and maintenance of the differentiated state. Interestingly, a strong association has been recently described between FOXE1 expression and susceptibility to thyroid cancer, but little is known about the mechanisms underlying FOXE1-induced thyroid tumorigenesis. Here, we used a panel of human thyroid cancer-derived cell lines covering the spectrum of thyroid cancer phenotypes to examine FOXE1 expression and to test for correlations between FOXE1 expression, the allele frequency of two SNPs and a length polymorphism in or near the FOXE1 locus associated with cancer susceptibility, and the migration ability of thyroid cancer cell lines. Results showed that FOXE1 expression correlated with differentiation status according to histological sub-type, but not with SNP genotype or cell migration ability. However, loss-and-gain-of-function experiments revealed that FOXE1 modulates cell migration, suggesting a role in epithelial-to-mesenchymal transition (EMT). Our previous genome-wide expression analysis identified Zeb1, a major EMT inducer, as a putative Foxe1 target gene. Indeed, gene silencing of FOXE1 decreased ZEB1 expression, whereas its overexpression increased ZEB1 transcriptional activity. FOXE1 was found to directly interact with the ZEB1 promoter. Lastly, ZEB1 silencing decreased the ability of thyroid tumoral cells to migrate and invade, pointing to its importance in thyroid tumor mestastases. In conclusion, we have identified ZEB1 as a bona fide target of FOXE1 in thyroid cancer cells, which provides new insights into the role of FOXE1 in regulating cell migration and invasion in thyroid cancer.

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Proteomic analysis of human thyroid cell lines reveals reduced nuclear localization of Mn-SOD in poorly differentiated thyroid cancer cells

Journal of Endocrinological Investigation ◽

10.1007/bf03345356 ◽

2005 ◽

Vol 28 (4) ◽

pp. 137-144 ◽

Cited By ~ 12

Author(s):

D. Russo ◽

A. Bisca ◽

M. Celano ◽

F. Talamo ◽

F. Arturi ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Nuclear Localization ◽

Proteomic Analysis ◽

Differentiated Thyroid Cancer ◽

Human Thyroid ◽

Thyroid Cell ◽

Poorly Differentiated ◽

Thyroid Cancer Cells

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Metformin Reverts the Secretion of CXCL8 Induced by TNF-α in Primary Cultures of Human Thyroid Cells: An Additional Indirect Anti-Tumor Effect of the Drug

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-3045 ◽

2015 ◽

Vol 100 (3) ◽

pp. E427-E432 ◽

Cited By ~ 22

Author(s):

Mario Rotondi ◽

Francesca Coperchini ◽

Patrizia Pignatti ◽

Flavia Magri ◽

Luca Chiovato

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Primary Cultures ◽

Human Thyroid ◽

Thyroid Cells ◽

Cxcl8 Secretion ◽

Tnf Α ◽

Thyroid Cancer Cell Lines ◽

Thyroid Cancer Cells

Context: Metformin displays both direct and indirect anti-tumor effects. CXCL8 is a crucial downstream mediator of Nuclear-Factor-κB signaling related to the growth and progression of thyroid cancers. Targeting CXCL8 results in prolonged survival and reduced metastatic spread in in-vivo animal models of thyroid tumors. Objective: This study aimed to evaluate whether metformin inhibits the secretion of CXCL8 induced by Tumor-Necrosis-Factor-α (TNF-α) in primary cultures of normal and tumor human thyroid cells as well as in thyroid cancer cell lines. Methods: Normal human thyrocytes, papillary thyroid cancer cells, and thyroid cancer cell lines (TPC-1 and BCPAP) were stimulated with TNF-α (10 ng/mL) alone or in combination with metformin (0.01, 0.1, 1, 2.5, 5, and 10mM). CXCL8 levels were measured in the cell supernatants after 24 hours. Results: Metformin significantly and dose-dependently inhibited the TNF-α-induced CXCL8 secretion in both normal thyrocytes (ANOVA: F = 42.04; P < .0001) and papillary thyroid cancer cells (ANOVA: F = 21.691; P < .0001) but not in TPC-1 and BCPAP cell lines. Conclusion: Metformin inhibits the TNF-α-induced CXCL8 secretion in primary cultures of normal thyroid cells and differentiated thyroid cancer cells at least of the most frequent poorly aggressive phenotype. The recruitment of neutrophils within the thyroid gland is a crucial metastasis-promoting factor, and it depends on the amount of CXCL8 produced by both tumor cells and by the more abundant normal thyroid cells exposed to TNF-α. Thus, the here-reported inhibiting effect of metformin on TNF-α-induced CXCL8 secretion could be considered as a further indirect anticancer property of the drug.

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Anti-proliferative effects of evodiamine on human thyroid cancer cells

Endocrine Abstracts ◽

10.1530/endoabs.35.p1094 ◽

2014 ◽

Author(s):

Ying-Ray Lee ◽

Chieh-Hsiang Lu ◽

Yi-Sheng Chang ◽

Yi-Wen Liu

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Human Thyroid ◽

Thyroid Cancer Cells

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Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space

International Journal of Molecular Sciences ◽

10.3390/ijms22042132 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2132

Author(s):

Petra M. Wise ◽

Paolo Neviani ◽

Stefan Riwaldt ◽

Thomas Juhl Corydon ◽

Markus Wehland ◽

...

Keyword(s):

Thyroid Cancer ◽

Protein Expression ◽

Cancer Cells ◽

Prolonged Exposure ◽

Space Station ◽

Surface Protein ◽

Surface Expression ◽

Human Thyroid ◽

Gene And Protein Expression ◽

Thyroid Cancer Cells

Space travel has always been the man’s ultimate destination. With the ability of spaceflight though, came the realization that exposure to microgravity has lasting effects on the human body. To counteract these, many studies were and are undertaken, on multiple levels. Changes in cell growth, gene, and protein expression have been described in different models on Earth and in space. Extracellular vesicles, and in particular exosomes, are important cell-cell communicators, being secreted from almost all the cells and therefore, are a perfect target to further investigate the underlying reasons of the organism’s adaptations to microgravity. Here, we studied supernatants harvested from the CellBox-1 experiment, which featured human thyroid cancer cells flown to the International Space Station during the SpaceX CRS-3 cargo mission. The initial results show differences in the number of secreted exosomes, as well as in the distribution of subpopulations in regards to their surface protein expression. Notably, alteration of their population regarding the tetraspanin surface expression was observed. This is a promising step into a new area of microgravity research and will potentially lead to the discovery of new biomarkers and pathways of cellular cross-talk.

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Protein Kinase A-Independent Inhibition of Proliferation and Induction of Apoptosis in Human Thyroid Cancer Cells by 8-Cl-Adenosine

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2331 ◽

2008 ◽

Vol 93 (3) ◽

pp. 1020-1029 ◽

Cited By ~ 15

Author(s):

Audrey J. Robinson-White ◽

Hui-Pin Hsiao ◽

Wolfgang W. Leitner ◽

Elizabeth Greene ◽

Andrew Bauer ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Thyroid Cancer ◽

Protein Kinase ◽

Protein Kinase A ◽

Cancer Cells ◽

Human Thyroid ◽

Inhibition Of Proliferation ◽

Thyroid Cancer Cells ◽

Kinase A

Abstract Purpose: Protein kinase A (PKA) affects cell proliferation in many cell types and is a potential target for cancer treatment. PKA activity is stimulated by cAMP and cAMP analogs. One such substance, 8-Cl-cAMP, and its metabolite 8-Cl-adenosine (8-Cl-ADO) are known inhibitors of cancer cell proliferation; however, their mechanism of action is controversial. We have investigated the antiproliferative effects of 8-Cl-cAMP and 8-CL-ADO on human thyroid cancer cells and determined PKA’s involvement. Experimental Design: We employed proliferation and apoptosis assays and PKA activity and cell cycle analysis to understand the effect of 8-Cl-ADO and 8-Cl-cAMP on human thyroid cancer and HeLa cell lines. Results: 8-Cl-ADO inhibited proliferation of all cells, an effect that lasted for at least 4 d. Proliferation was also inhibited by 8-Cl-cAMP, but this inhibition was reduced by 3-isobutyl-1-methylxanthine; both drugs stimulated apoptosis, and 3-isobutyl-1-methylxanthine drastically reduced 8-Cl-cAMP-induced cell death. 8-Cl-ADO induced cell accumulation in G1/S or G2/M cell cycle phases and differentially altered PKA activity and subunit levels. PKA stimulation or inhibition and adenosine receptor agonists or antagonists did not significantly affect proliferation. Conclusions: 8-Cl-ADO and 8-Cl-cAMP inhibit proliferation, induce cell cycle phase accumulation, and stimulate apoptosis in thyroid cancer cells. The effect of 8-Cl-cAMP is likely due to its metabolite 8-Cl-ADO, and PKA does not appear to have direct involvement in the inhibition of proliferation by 8-Cl-ADO. 8-Cl-ADO may be a useful therapeutic agent to be explored in aggressive thyroid cancer.

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