scholarly journals Nelfinavir inhibits proliferation and induces DNA damage in thyroid cancer cells

2017 ◽  
Vol 24 (3) ◽  
pp. 147-156 ◽  
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.

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

2020 ◽  
Vol 27 (3) ◽  
pp. 137-151 ◽  
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.

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

2017 ◽  
Vol 6 (7) ◽  
pp. 469-478 ◽  
Author(s):  
Joanna Klubo-Gwiezdzinska ◽  
John Costello ◽  
Kirk Jensen ◽  
Aneeta Patel ◽  
Rok Tkavc ◽  
...  
Keyword(s):  
Dna Damage ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Active Form ◽  
Human Thyroid ◽  
Parp Cleavage ◽  
Γ Radiation ◽  
Dna Damaging Agents ◽  
Thyroid Cancer Cells

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.

scholarly journals BAG3 Promoted Starvation-Induced Apoptosis of Thyroid Cancer Cells via Attenuation of Autophagy

2014 ◽  
Vol 99 (11) ◽  
pp. E2298-E2307 ◽  
Author(s):  
Si Li ◽  
Hai-Yan Zhang ◽  
Tian Wang ◽  
Xin Meng ◽  
Zhi-Hong Zong ◽  
...  
Keyword(s):  
Cell Death ◽  
Thyroid Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Real Time ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Complete Medium ◽  
Induced Apoptosis ◽  
Thyroid Cancer Cells

Context: BAG3 plays a regulatory role in a number of cellular processes. Recent studies have attracted much attention on its role in activation of selective autophagy. In addition, we have very recently reported that BAG3 is implicated in a BECN1-independent autophagy, namely noncanonical autophagy. Objective: The current study aimed to investigate the potential involvement of BAG3 in canonical autophagy triggered by Earle's Balanced Salt Solution (EBSS) starvation. Setting and Design: Replacement of complete medium with EBSS was used to trigger canonical autophagy. BAG3 expression was measured using real-time RT-PCR and Western blot. Autophagy was monitored using LC3-II transition and p62/SQSTM1 accumulation by Western blot, as well as punctate distribution of LC3 by immunofluorescence staining. Cell growth and apoptotic cell death was investigated using real-time cell analyzer and flowcytometry, respectively. Results: BAG3 expression was potently reduced by EBSS starvation. Forced expression of BAG3 suppressed autophagy and promoted apoptotic cell death of thyroid cancer cells elicited by starvation. In addition, in the presence of autophagy inhibitor, the enhancing effect of BAG3 on apoptotic cell death was attenuated. Conclusions: These results suggest that BAG3 promotes apoptotic cell death in starved thyroid cancer cells, at least in part by autophagy attenuation.

scholarly journals Autophagy and thyroid carcinogenesis: genetic and epigenetic links

2013 ◽  
Vol 21 (1) ◽  
pp. R13-R29 ◽  
Author(s):  
Federica Morani ◽  
Rossella Titone ◽  
Loredana Pagano ◽  
Alessandra Galetto ◽  
Oscar Alabiso ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Endocrine System ◽  
Good Prognosis ◽  
Thyroid Cancers ◽  
Radioiodine Ablation ◽  
Well Differentiated ◽  
Papillary Type ◽  
Thyroid Cancer Cells

Thyroid cancer is the most common cancer of the endocrine system and is responsible for the majority of deaths from endocrine malignancies. Although a large proportion of thyroid cancers belong to well differentiated histologic subtypes, which in general show a good prognosis after surgery and radioiodine ablation, the treatment of radio-resistant papillary-type, of undifferentiated anaplastic, and of medullary-type thyroid cancers remains unsatisfactory. Autophagy is a vesicular process for the lysosomal degradation of protein aggregates and of damaged or redundant organelles. Autophagy plays an important role in cell homeostasis, and there is evidence that this process is dysregulated in cancer cells. Recentin vitropreclinical studies have indicated that autophagy is involved in the cytotoxic response to chemotherapeutics in thyroid cancer cells. Indeed, several oncogenes and oncosuppressor genes implicated in thyroid carcinogenesis also play a role in the regulation of autophagy. In addition, some epigenetic modulators involved in thyroid carcinogenesis also influence autophagy. In this review, we highlight the genetic and epigenetic factors that mechanistically link thyroid carcinogenesis and autophagy, thus substantiating the rationale for an autophagy-targeted therapy of aggressive and radio-chemo-resistant thyroid cancers.

scholarly journals Antitumor Effect of Various Phytochemicals on Diverse Types of Thyroid Cancers

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 125 ◽  
Author(s):  
Hye-Ji Shin ◽  
Kyung-A Hwang ◽  
Kyung-Chul Choi
Keyword(s):  
Thyroid Cancer ◽  
Animal Studies ◽  
Anaplastic Thyroid Cancer ◽  
Thyroid Cancers ◽  
Anticancer Efficacy ◽  
Other Substances ◽  
English Articles ◽  
Thyroid Cancer Cells ◽  
Inhibit Cell Proliferation

Thyroid cancers developed from the tissues of the thyroid gland are classified into papillary (PTC), follicular (FTC), medullary (MTC), and anaplastic thyroid cancer (ATC). Although thyroid cancers have been generally known as mild forms of cancer, undifferentiated MTC and ATC have a more unfavorable prognosis than differentiated PTC and FTC because they are more aggressive and early metastatic. A variety of therapies such as surgery, radiotherapy, and chemotherapy have been currently used to treat thyroid cancer, but they still have limitations including drug resistance or unfavorable side effects. Phytochemicals are plant-derived chemicals having various physiological activities that are expected to be effective in cancer treatment. In this review, anticancer efficacy of phytochemicals, such as resveratrol, genistein, curcumin, and other substances in each type of thyroid cancer was introduced with their chemopreventive mechanisms. English articles related with thyroid cancer and anti-thyroid cancer of phytochemicals were searched from PubMed and Google Scholar. This article mainly focused on in vitro or animal studies on phytochemicals with anti-thyroid cancer activity. These various phytochemicals have been shown to induce apoptosis in all types of thyroid cancer cells, inhibit cell proliferation and invasion, and to be helpful in enhancing the effect of radioiodine therapy that is a typical therapy to thyroid cancer. These results suggest that thyroid cancer can be more effectively treated by the combinations of phytochemicals and the existing therapies or substances.

Dual inhibition of BRAF and MEK increases expression of sodium iodide symporter in patient-derived papillary thyroid cancer cells in vitro

Surgery ◽  
2020 ◽  
Vol 167 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Timothy M. Ullmann ◽  
Heng Liang ◽  
Maureen D. Moore ◽  
Isra Al-Jamed ◽  
Katherine D. Gray ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Papillary Thyroid Cancer ◽  
Sodium Iodide ◽  
Papillary Thyroid ◽  
Sodium Iodide Symporter ◽  
Dual Inhibition ◽  
Thyroid Cancer Cells

LncRNA SNHG4 promotes the proliferation, migration, invasiveness, and epithelial–mesenchymal transition of lung cancer cells by regulating miR-98-5p

2019 ◽  
Vol 97 (6) ◽  
pp. 767-776 ◽  
Author(s):  
Yufu Tang ◽  
Lijian Wu ◽  
Mingjing Zhao ◽  
Guangdan Zhao ◽  
Shitao Mao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
Gene 4

Long noncoding RNA small nucleolar RNA host gene 4 (SNHG4) is usually up-regulated in cancer and regulates the malignant behavior of cancer cells. However, its role in lung cancer remains elusive. In this study, we silenced the expression of SNHG4 in NCI-H1437 and SK-MES-1, two representative non-small-cell lung cancer cell lines, by transfecting them with siRNA (small interfering RNA) that specifically targets SNHG4. We observed significantly inhibited cell proliferation in vitro and reduced tumor growth in vivo after SNHG4 silencing. SNHG4 knockdown also led to cell cycle arrest at the G1 phase, accompanied with down-regulation of cyclin-dependent kinases CDK4 and CDK6. The migration and invasiveness of these two cell lines were remarkably inhibited after SNHG4 silencing. Moreover, our study revealed that the epithelial–mesenchymal transition (EMT) of lung cancer cells was suppressed by SNHG4 silencing, as evidenced by up-regulated E-cadherin and down-regulated SALL4, Twist, and vimentin. In addition, we found that SNHG4 silencing induced up-regulation of miR-98-5p. MiR-98-5p inhibition abrogated the effect of SNHG4 silencing on proliferation and invasion of lung cancer cells. In conclusion, our findings demonstrate that SNHG4 is required by lung cancer cells to maintain malignant phenotype. SNHG4 probably exerts its pro-survival and pro-metastatic effects by sponging anti-tumor miR-98-5p.

scholarly journals Dual Oncogenic/Anti-Oncogenic Role of PATZ1 in FRTL5 Rat Thyroid Cells Transformed by the Ha-RasV12 Oncogene

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 127 ◽  
Author(s):  
Michela Vitiello ◽  
Giuseppe Palma ◽  
Mario Monaco ◽  
Anna Bello ◽  
Simona Camorani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Tumor Growth Rate ◽  
Stem Cell Markers ◽  
Thyroid Cells ◽  
Mesenchymal Transition ◽  
Rat Thyroid ◽  
The Impact ◽  
Thyroid Cancer Cells

PATZ1 is a transcriptional factor downregulated in thyroid cancer whose re-expression in thyroid cancer cells leads to a partial reversion of the malignant phenotype, including the capacity to proliferate, migrate, and undergo epithelial-to-mesenchymal transition. We have recently shown that PATZ1 is specifically downregulated downstream of the Ras oncogenic signaling through miR-29b, and that restoration of PATZ1 in Ha-Ras transformed FRTL5 rat thyroid cells is able to inhibit their capacities to proliferate and migrate in vitro. Here, we analyzed the impact of PATZ1 expression on the in vivo tumorigenesis of these cells. Surprisingly, FRTL5-Ras-PATZ1 cells showed enhanced tumor initiation when engrafted in nude mice, even if their tumor growth rate was reduced compared to that of FRTL5-Ras control cells. To further investigate the cause of the enhanced tumor engraftment of FRTL5-Ras-PATZ1 cells, we analyzed the stem-like potential of these cells through their capacity to grow as thyrospheres. The results showed that restoration of PATZ1 expression in these cells increases stem cell markers’ expression and self-renewal ability of the thyrospheres while limiting their growth capacity. Therefore, we suggest that PATZ1 may play a role in enhancing the stem cell potential of thyroid cancer cells, but, at the same time, it impairs the proliferation of non-stem cells.

scholarly journals Effects of sorafenib and an adenylyl cyclase activator on in vitro growth of well-differentiated thyroid cancer cells

2017 ◽  
Vol 64 (11) ◽  
pp. 1115-1123 ◽  
Author(s):  
Aya Sawa ◽  
Tomohiro Chiba ◽  
Jun Ishii ◽  
Hiroyuki Yamamoto ◽  
Hisato Hara ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Adenylyl Cyclase ◽  
Cancer Cells ◽  
Differentiated Thyroid Cancer ◽  
Well Differentiated ◽  
Thyroid Cancer Cells ◽  
Cyclase Activator
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