Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models

Background Amifostine is a potent scavenger of reactive oxygen species that is used for the salivary gland protection during therapy with radioactive iodine for thyroid cancer. There are no data on the potential effect of amifostine on thyroid cancer cells. Methods We investigated the effects of the active form of amifostine (WR-1065) on the response of thyroid cancer cells to treatment with DNA-damaging agents. WR-1065 was examined in human thyroid cancer cell lines (FTC133, TPC1, BCPAP and C643) and embryonic fibroblast cells NIH3T3. DNA damage was induced by exposure to H2O2 (0.1 mM), by treatment with the radiomimetic neocarzinostatin (NCS 250 ng/mL) and by γ-radiation (6 Gy). DNA damage, cell viability and apoptosis were examined. Results We demonstrated the selective action of WR-1065 (0.1 mM), which prevented oxidative stress–induced DNA damage in fibroblasts, but did not protect thyroid cancer cells from DNA damage and apoptosis documented by caspase-3 and PARP cleavage after exposure to H2O2, NCS and γ-radiation. Prolonged exposure to WR-1065 (0.1 mM for 24 h) was toxic for thyroid cancer cells; this treatment decreased the number of viable cells by 8% in C643 cells, 47% in TPC cells, 92% in BCPAP cells and 82% in FTC 133 cells. The cytotoxic effects of WR-1065 were not associated with induction of apoptosis. Conclusions Our data show that amifostine has no protective effect on thyroid cancer cells against DNA-damaging agents in vitro and suggest that amifostine will not attenuate the efficacy of radioiodine treatment in patients with thyroid cancer.

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Inhibition of gap junction transfer sensitizes thyroid cancer cells to anoikis

Endocrine Related Cancer ◽

10.1530/erc-10-0289 ◽

2011 ◽

Vol 18 (5) ◽

pp. 613-626 ◽

Cited By ~ 16

Author(s):

Kirk Jensen ◽

Aneeta Patel ◽

Joanna Klubo-Gwiezdzinska ◽

Andrew Bauer ◽

Vasyl Vasko

Keyword(s):

Thyroid Cancer ◽

Gap Junction ◽

Cancer Cells ◽

Cancer Cell ◽

Thyroid Tissue ◽

Human Thyroid ◽

Thyroid Cancer Cell ◽

Gap Junctional ◽

Thyroid Cancer Cells

Resistance to anoikis (matrix deprivation-induced apoptosis) is a critical component of the metastatic cascade. Molecular mechanisms underlying resistance to anoikis have not been reported in thyroid cancer cells. For an in vitro model of anoikis, we cultured follicular, papillary, and anaplastic thyroid cancer cell lines on poly-HEMA-treated low-adherent plates. We also performed immunohistochemical analysis of human cancer cells that had infiltrated blood and/or lymphatic vessels. Matrix deprivation was associated with establishment of contacts between floating thyroid cancer cells and formation of multi-cellular spheroids. This process was associated with activation of gap junctional transfer. Increased expression of the gap junction molecule Connexin43 was found in papillary and anaplastic cancer cells forming spheroids. All non-adherent cancer cells showed a lower proliferation rate compared with adherent cells but were more resistant to serum deprivation. AKT was constitutively activated in cancer cells forming spheroids. Inhibition of gap junctional transfer through Connexin43 silencing, or by treatment with the gap junction disruptor carbenoxolone, resulted in loss of pAKT and induction of apoptosis in a cell-type-specific manner. In human thyroid tissue, cancer cells that had infiltrated blood vessels showed morphological similarity to cancer cells forming spheroids in vitro. Intra-vascular cancer cells demonstrated prominent AKT activation in papillary and follicular cancers. Increased Connexin43 immunoreactivity was observed only in intra-vascular papillary cancer cells. Our data demonstrate that establishment of inter-cellular communication contributes to thyroid cancer cell resistance to anoikis. These findings suggest that disruption of gap junctional transfer could represent a potential therapeutic strategy for prevention of metastases.

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Nelfinavir inhibits proliferation and induces DNA damage in thyroid cancer cells

Endocrine Related Cancer ◽

10.1530/erc-16-0568 ◽

2017 ◽

Vol 24 (3) ◽

pp. 147-156 ◽

Cited By ~ 12

Author(s):

Kirk Jensen ◽

Athanasios Bikas ◽

Aneeta Patel ◽

Yevgeniya Kushchayeva ◽

John Costello ◽

...

Keyword(s):

Dna Damage ◽

Thyroid Cancer ◽

Cancer Cells ◽

Real Time ◽

Cell Lines ◽

Apoptotic Cell ◽

Thyroid Cancers ◽

Mesenchymal Transition ◽

Thyroid Cancer Cells

The HIV protease inhibitor Nelfinavir (NFV) inhibits PI3K/AKT and MAPK/ERK signaling pathways, emerging targets in thyroid cancers. We examined the effects of NFV on cancer cells that derived from follicular (FTC), papillary (PTC) and anaplastic (ATC) thyroid cancers. NFV (1–20 µM) was tested in FTC133, BCPAP and SW1736 cell lines. The effects of NFV on cell proliferation were determined in vitro using real-time microscopy and by flow cytometry. DNA damage, apoptotic cell death and expression of molecular markers of epithelial–mesenchymal transition (EMT) were determined by Western blot and real-time PCR. Real-time imaging demonstrated that NFV (10 µM) increased the time required for the cell passage through the phases of cell cycle and induced DNA fragmentation. Growth inhibitory effects of NFV were associated with the accumulation of cells in G0/G1 phase, downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). NFV also induced the expression of γH2AX and p53BP1 indicating DNA damage. Treatment with NFV (20 µM) resulted in caspase-3 cleavage in all examined cells. NFV (20 µM) decreased the levels of total and p-AKT in PTEN-deficient FTC133 cells. NFV had no significant effects on total ERK and p-ERK in BRAF-positive BCPAP and SW1736 cells. NFV had no effects on the expression of EMT markers (Twist, Vimentin, E- and N-Cadherin), but inhibited the migration and decreased the abilities of thyroid cancer cells to survive in non-adherent conditions. We conclude that NFV inhibits proliferation and induces DNA damage in thyroid cancer cell lines. Our in vitro data suggest that NFV has a potential to become a new thyroid cancer therapeutic agent.

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Evodiamine inhibits human thyroid cancer cells in vitro and in vivo

Endocrine Abstracts ◽

10.1530/endoabs.37.ep902 ◽

2015 ◽

Cited By ~ 1

Author(s):

Ying-Ray Lee ◽

Chieh-Hsiang Lu ◽

Yi-Sheng Chang ◽

Shu-Hsin Chen ◽

Yi-Wen Liu

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Human Thyroid ◽

Thyroid Cancer Cells

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In Vitro Antitumor Activity of Aloperine on Human Thyroid Cancer Cells through Caspase-Dependent Apoptosis

International Journal of Molecular Sciences ◽

10.3390/ijms19010312 ◽

2018 ◽

Vol 19 (1) ◽

pp. 312 ◽

Cited By ~ 13

Author(s):

Ying-Ray Lee ◽

Shu-Hsin Chen ◽

Ching-Yen Lin ◽

Wen-Ying Chao ◽

Yun-Ping Lim ◽

...

Keyword(s):

Thyroid Cancer ◽

Antitumor Activity ◽

Cancer Cells ◽

Human Thyroid ◽

Thyroid Cancer Cells

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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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