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 Induction of apoptosis and necrosis by zinc in human thyroid cancer cell lines

2001 ◽  
Vol 169 (2) ◽  
pp. 417-424 ◽  
Author(s):  
M Iitaka ◽  
S Kakinuma ◽  
S Fujimaki ◽  
I Oosuga ◽  
T Fujita ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Thyroid ◽  
Dependent Manner ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cell Lines ◽  
Thyroid Cancer Cells

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.

scholarly journals Selenite Induces Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species-Dependent Inhibition of the AKT/mTOR Pathway in Thyroid Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhen Cheng ◽  
Shuang Yu ◽  
Weiman He ◽  
Jie Li ◽  
Tianyi Xu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Thyroid Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Sodium Selenite ◽  
Oxygen Species ◽  
Cycle Arrest ◽  
Intracellular Ros ◽  
Thyroid Cancer Cells

Thyroid cancer is the most common endocrine malignancy, and its incidence has increased in the past decades. Selenium has been shown to have therapeutic effects against several tumors. However, its role in thyroid cancer and its underlying molecular mechanism remains to be explored. In the present study, we demonstrated that sodium selenite significantly decreased cell viability and induced G0/G1 cell cycle arrest and apoptosis in thyroid cancer cells in a dose-dependent manner. Transcriptomics revealed that sodium selenite induced intracellular reactive oxygen species (ROS) by promoting oxidative phosphorylation. Increased intracellular ROS levels inhibited the AKT/mTOR signaling pathway and upregulated EIF4EBP3. Intracellular ROS inhibition by N-acetylcysteine (NAC) ameliorated the cellular effects of sodium selenite. The in vitro findings were reproduced in xenograft thyroid tumor models. Our data demonstrated that sodium selenite exhibits strong anticancer effects against thyroid cancer cells, which involved ROS-mediated inhibition of the AKT/mTOR pathway. This suggests that sodium selenite may serve as a therapeutic option for advanced thyroid cancer.

scholarly journals Valproic Acid Induces Apoptosis and Cell Cycle Arrest in Poorly Differentiated Thyroid Cancer Cells

2005 ◽  
Vol 90 (3) ◽  
pp. 1383-1389 ◽  
Author(s):  
Maria G. Catalano ◽  
Nicoletta Fortunati ◽  
Mariateresa Pugliese ◽  
Lucia Costantino ◽  
Roberta Poli ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Valproic Acid ◽  
Thyroid Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Differentiated Thyroid Cancer ◽  
Cycle Arrest ◽  
Poorly Differentiated ◽  
Thyroid Cancer Cells

scholarly journals Study On the Antitumor Bioactivity of Koningic Acid in Thyroid Cancer in Vivo and in Vitro

2021 ◽  
Author(s):  
Changxin Jing ◽  
Yanyan Li ◽  
Zhifei Gao ◽  
Peng Hou ◽  
Rong Wang
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colony Formation ◽  
Control Group ◽  
Dependent Manner ◽  
Thyroid Cancer Cell ◽  
Xenograft Tumor ◽  
Antitumor Effects ◽  
Thyroid Cancer Cells

Abstract Purpose: Koningic acid (KA), a sesquiterpene lactone, has been identified as an antimicrobial agent. Recent studies have revealed KA’s antitumor activities in colorectal cancer, leukemia, and lung cancer. However, its antitumor effect in thyroid cancer remains largely unknown. The aim of this study is to test the therapeutic potential of KA in thyroid cancer and explore the mechanisms underlying antitumor effects.Methods: We examined the effects of KA on proliferation, colony formation, apoptosis, ATP deprivation, and xenograft tumor growth in thyroid cancer cells.Results: KA inhibited thyroid cancer cell proliferation, colony formation, and induced cell apoptosis in a dose and time-dependent manner. Our data also showed that KA caused a rapid, extensive decrease of ATP levels in thyroid cancer cells. Growth of xenograft tumor derived from the thyroid cancer cell line C643 in nude mice was significantly inhibited by KA. Importantly, KA treatment did not cause significant liver and kidney damage in mice compared with the control group.Conclusion: KA may be used as an effective and safe agent for thyroid cancer treatment.

scholarly journals Heme Oxygenase-1 Inhibitors Induce Cell Cycle Arrest and Suppress Tumor Growth in Thyroid Cancer Cells

2018 ◽  
Vol 19 (9) ◽  
pp. 2502 ◽  
Author(s):  
Po-Sheng Yang ◽  
Yi-Chiung Hsu ◽  
Jie-Jen Lee ◽  
Ming-Jen Chen ◽  
Shih-Yuan Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
G1 Arrest ◽  
Cycle Arrest ◽  
Thyroid Cancer Cells

Heme oxygenase-1 (HO-1) is induced by a variety of stimuli and plays a multifaceted role in cellular protection. We have shown that HO-1 is overexpressed in thyroid cancer and is associated with tumor aggressiveness. Therefore, we set out to assess the effects of HO-1 inhibitors on the biology of thyroid cancer cells. Two different classes of HO-1 inhibitors were used, including a metalloporphyrin, zinc protoporphyrin-IX (ZnPP), and an azole antifungal agent, ketoconazole. The viability and colony formation of thyroid cancer cells decreased in a concentration- and time-dependent fashion following treatment with HO-1 inhibitors. Cancer cells exhibited a higher sensitivity to HO-1 inhibitors than non-malignant cells. HO-1 inhibitors induced a G0/G1 arrest accompanied by decreased cyclin D1 and CDK4 expressions and an increase in levels of p21 and p27. HO-1 inhibitors significantly increased intracellular ROS levels and suppressed cell migration and invasion. Oxygen consumption rate and mitochondrial mass were increased with ZnPP treatment. Mice treated with ZnPP had a reduced xenograft growth and diminished cyclin D1 and Ki-67 staining in tumor sections. Taken together, HO-1 inhibitors might have therapeutic potential for inducing cell cycle arrest and promoting growth suppression of thyroid cancer cells in vitro and in vivo.

scholarly journals Chlorotoxin Conjugated with Saporin Reduces Viability of ML-1 Thyroid Cancer Cells In Vitro

2019 ◽  
Author(s):  
Husref Rizvanovic ◽  
A Daniel Pinheiro ◽  
Kyoungtae Kim ◽  
Johnson Thomas
Keyword(s):  
Thyroid Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Unmet Need ◽  
Matrix Metalloproteinase 2 ◽  
Dependent Manner ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cells

AbstractBackgroundAlthough differentiated thyroid cancer has good prognosis, radioactive iodine (RAI) resistant thyroid cancer is difficult to treat. Current therapies for progressive RAI resistant thyroid cancer are not very effective. There is an unmet need for better therapeutic agents in this scenario. Studies have shown that aggressive thyroid cancers express matrix metalloproteinase −2 (MMP-2). Chlorotoxin is a selective MMP-2 agonist. Given that Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment, we hypothesized that Chlorotoxin-conjugated Saporin (CTX-SAP) would inhibit the growth of aggressive thyroid cancer cell lines expressing MMP-2.MethodsThe ML-1 thyroid cancer cell line was used for this study because it is known to express MMP-2. ML-1 cells were treated with a toxin consisting of biotinylated Chlorotoxin bonded with a secondary conjugate of Streptavidin-ZAP containing Saporin (CTX-SAP) from 0 to 600 nM for 72 hours. Then, cell viability was measured via XTT assay at an absorbance of A450-630. Control experiments were set up using Chlorotoxin and Saporin individually at the same varying concentrations.ResultsAfter 7 hours of incubation, there was a statistically significant reduction in cell viability with increasing concentrations of the CTX-SAP conjugate (F=4.286, p=0.0057). In particular, the cell viability of ML-1 cells was decreased by 49.77% with the treatment of 600 nM of CTX-SAP (F=44.24), and the reduction in cell viability was statistically significant (Dunnett’s test p<0.0001). In contrast, individual Chlorotoxin or Saporin in increasing concentrations had no significant effect on cell viability using similar assay.ConclusionThis in vitro study demonstrated the efficacy of a CTX-SAP conjugate in reducing the viability of ML-1 thyroid cancer cells in a dose dependent manner. Further studies are needed to delineate the effectiveness of CTX-SAP in the treatment of aggressive thyroid cancer. Our study points towards MMP-2 as a potential target for RAI-resistant thyroid cancer.

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