scholarly journals Quantitative High-Throughput Drug Screening Identifies Novel Classes of Drugs with Anticancer Activity in Thyroid Cancer Cells: Opportunities for Repurposing

2012 ◽  
Vol 97 (3) ◽  
pp. E319-E328 ◽  
Author(s):  
Lisa Zhang ◽  
Mei He ◽  
Yaqin Zhang ◽  
Naris Nilubol ◽  
Min Shen ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
High Throughput ◽  
Drug Screening ◽  
High Throughput Drug Screening ◽  
Thyroid Cancer Cells

scholarly journals Quercetin Induces Anticancer Activity by Upregulating Pro-NAG-1/GDF15 in Differentiated Thyroid Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3022
Author(s):  
Yukyung Hong ◽  
Jaehak Lee ◽  
Hyunjin Moon ◽  
Chang H. Ryu ◽  
Jungirl Seok ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cancer Prognosis ◽  
Antibody Array ◽  
Dependent Manner ◽  
Normal Tissues ◽  
Cycle Arrest ◽  
Novel Biomarkers ◽  
Thyroid Cancer Cells

Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBPα, or C/EBPδ played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.

scholarly journals Anti-proliferative mechanism of Huaier extract in human thyroid carcinoma cells

2020 ◽  
Author(s):  
Jingni He ◽  
Ying Zhang ◽  
Lidong Wang ◽  
Yifang Yu ◽  
Baiyu Yao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Treated Group ◽  
G1 Phase ◽  
Thyroid Cancer Cells ◽  
Number Of Cells

Abstract BackgroundThyroid cancer is the most common endocrine tumor and typically has a good prognosis; however, some patients still present with local or distant metastases. Huaier is a traditional Chinese medicine reported as effective in treating certain types of tumor, but the effect of Huaier on thyroid cancer has not yet been reported. MethodsThe thyroid cancer cell lines, B-CPAP and C643, were treated with increasing concentrations of Huaier extract and the therapeutic effect was measured using a cell counting kit 8 (CCK-8) and flow cytometry. High-throughput sequencing was further performed to identify differentially expressed genes (DEGs) in Huaier-treated B-CPAP cells. Moreover, quantitative real-time PCR (RT-qPCR) was carried out to verify the selected RNAs. Finally, the dual luciferase detection kit was used to detect gene activity.ResultsProliferation of B-CPAP and C643 cells was significantly suppressed by treatment with Huaier extract in a concentration- and time-dependent manner. Huaier extract also induced cell cycle arrest and apoptosis according to flow cytometry (p < 0.05).High-throughput sequencing observed 7,979 significantly altered transcripts. Gene Ontology (GO) analysis showed that 270 genes were enriched in upregulated terms, while 171 genes were enriched in downregulated terms (p < 0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that there were 47 enriched pathways associated with DEGs (p < 0.05). The expression levels of chosen lncRNAs (SNHG7, MIR181A2HG, ILF3-AS1, and CTA-29F11.1) and their corresponding mRNAs (BBC3, CTSL, GADD45A, and DDIT3) were verified to be overexpressed in Huaier-treated B-CPAP cells by RT-qPCR (p < 0.05).Following transduction, the CCK-8 results showed that the proliferative capacity was increased in the shRNA group as compared with that in the Ctrl and Scr groups. According to flow cytometry, the number of cells in the G0/G1 phase was decreased in the shRNA group (p < 0.01) and the apoptosis rate was lower (p < 0.05). The shRNA-treated group had significantly reduced Huaier-induced apoptosis as compared with the Scr-treated group (p < 0.05). Moreover, the number of cells in the G0/G1 phase in the shRNA-treated group was significantly lower than that in the Scr-treated group (p < 0.05). The results of the dual luciferase reporter gene experiment showed that the activity in the GADD45A WT + miR-301a-3p(+) group was significantly reduced as compared with that in the GADD45A WT + miR-301a-3p(+) NC group (p < 0.01). Further, the activity in the ILF3-AS1 WT + miR-301a-3p(+) group was significantly lower than that in the ILF3-AS1 WT + miR-301a-3p(+) NC group (p < 0.05).ConclusionsThe present study demonstrates that Huaier extract inhibits the proliferation of thyroid cancer cells via changes in the expression levels of a multitude of genes. In particular, a decrease in GADD45A expression enhances the proliferative ability of thyroid cancer cells, the levels of which can be increased by Huaier treatment, thus regulating the cell cycle and apoptosis. Huaier can inhibit the proliferation of thyroid cancer cells through the ILF3-AS1/hsa-miR-301a-3p/GADD45A ceRNA axis.

scholarly journals OR28-03 Drug Repurposing Identifies Inhibitors of the Proteostasis Network to Augment Radioiodine Uptake in Combinatorial Approaches Targeting Thyroid Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Martin L Read ◽  
Katie Brookes ◽  
Alice Fletcher ◽  
Caitlin E M Thornton ◽  
Mohammed Alshahrani ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
High Throughput ◽  
High Throughput Screening ◽  
Drug Repurposing ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Radioiodine Uptake ◽  
Repurposed Drugs ◽  
Thyroid Cancer Cells

Abstract New combinatorial drug strategies are urgently needed to improve radioiodine (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. Drug repurposing offers the promise of identifying already approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. However, a lack of thyroid cell-based assays amenable to high-throughput screening has limited progress. We utilised the mutated yellow fluorescent protein (YFP) as a surrogate biosensor of intracellular iodide and screened the Prestwick Chemical Library (1200 drugs; 95% approved) for quenching of YFP fluorescence. This allowed us to identify putative candidate drugs which increased iodide uptake &gt;2 SD above mean. Categorisation of these revealed a high proportion of drugs that modulate the proteostasis network (19/48; ~40%), including key processes in protein homeostasis such as endoplasmic reticulum-associated protein degradation (ERAD) and autophagy. Secondary screening validated the activity of proteostasis modulators in enhancing iodide uptake after ranking 73 leading compounds based on their pharmacologic (AUC, EMAX and EC50) and specificity of response (NIS+ve vs NIS-ve YFP-thyroid cells) at ten different drug doses (0.1 to 50 μM). Of importance, several repurposed drugs (e.g. ebastine, Prestwick N, Prestwick C and clotrimazole) in combination with the HDAC inhibitor vorinostat induced a robust enhancement in RAI uptake in thyroid cancer cells (TPC-1 and 8505C NIS+ve cells, up to 11-fold vs DMSO, P&lt;0.001), which was significantly greater than using vorinostat alone (up to 3-fold, P&lt;0.01). For clotrimazole, we designed 7 new chemical derivatives, 3 of which showed enhanced aqueous solubility and retained the ability to significantly enhance RAI uptake. TaqMan RT-PCR revealed that, in contrast to vorinostat, our repurposed drugs failed to alter NIS mRNA expression, highlighting post-transcriptional mechanisms. Critically, 11 repurposed drugs induced significant gains in RAI uptake in human primary thyroid cells (up to 4.1-fold; P&lt;0.05), the most physiological setting for NIS function. In conclusion, we performed high-throughput screening and identified proteostasis modulators, as well as other repurposed drugs, that markedly enhance radioiodine uptake. Further clinical investigation of these drugs might offer new combinatorial approaches, especially with existing therapies, to improve the treatment of thyroid cancer.

High-Throughput Drug Screening of FDA-Approved Cancer Drugs Reveals Novel Therapies for Patients with Chordomas

2019 ◽  
Author(s):  
Philip Tatman ◽  
Anthony Fringuello ◽  
Denise Damek ◽  
Samy Youssef ◽  
Randy Jensn ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Novel Therapies ◽  
Cancer Drugs ◽  
High Throughput Drug Screening

High-Throughput Drug Screening of ECM Deposition Inhibitors for Antifibrotic Drug Discovery

2019 ◽  
Author(s):  
Michael Gerckens ◽  
Hani Alsafadi ◽  
Darcy Wagner ◽  
Katharina Heinzelmann ◽  
Kenji Schorpp ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
Drug Screening ◽  
High Throughput Drug Screening
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