scholarly journals 4-IPP, a selective MIF inhibitor, causes mitotic catastrophe in thyroid carcinomas

2015 ◽  
Vol 22 (5) ◽  
pp. 759-775 ◽  
Author(s):  
Luca Varinelli ◽  
Dario Caccia ◽  
Chiara C Volpi ◽  
Claudio Caccia ◽  
Maida De Bortoli ◽  
...  
Keyword(s):  
Cell Death ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Thyroid Neoplasms ◽  
Mitotic Cell ◽  
Resistant Cell ◽  
Anaplastic Thyroid Carcinoma ◽  
Mitotic Catastrophe ◽  
Important Player ◽  
Cell Subpopulations

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is over-expressed in several human neoplastic cells. When MIF binds its receptor (CD74) and co-receptor (CD44), it initiates signaling cascades that orchestrate cell proliferation and survival, and it can directly modulate the activity of AMPK. These activities indicate that MIF potentially regulates cell survival and metabolism. We found that MIF was primarily co-expressed with CD74 in 16 out of 23 papillary thyroid carcinoma (PTC) and in all the 27 available anaplastic thyroid carcinoma (ATC) biopsy samples. MIF and CD74 were co-expressed in TPC-1 and HTC-C3 cell lines. The selective MIF inhibitor, 4-iodo-6-phenylpyrimidine (4-IPP), blocked MIF/CD74 internalization, activated JNK, and dose-dependently inhibited proliferation inducing apoptosis and mitotic cell death. In two CD74-negative cell lines, NIM-1 and K1, 4-IPP treatment partially reduced proliferation. Coordinated MIF and CD74 expression appeared to confer in tumor cells the plasticity necessary to escape cell cycle regulation, metabolic changes, and stress conditions. MIF/CD74 signaling removal made cells susceptible to apoptosis and mitotic cell death. This finding suggests a possible avenue for targeting DNA endoreduplication, thus preventing the proliferation of therapy-resistant cell subpopulations. This study highlights MIF/CD74 axis as an important player in the biology of aggressive thyroid neoplasms.

scholarly journals ONYX-015, an E1B Gene-Defective Adenovirus, Induces Cell Death in Human Anaplastic Thyroid Carcinoma Cell Lines

2002 ◽  
Vol 87 (6) ◽  
pp. 2525-2531 ◽  
Author(s):  
Giuseppe Portella ◽  
Stefania Scala ◽  
Donata Vitagliano ◽  
Giancarlo Vecchio ◽  
Alfredo Fusco
Keyword(s):  
Cell Death ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
P53 Gene ◽  
Anaplastic Thyroid Carcinoma ◽  
Anaplastic Carcinoma ◽  
Human Thyroid ◽  
Innovative Therapy ◽  
Carcinoma Cell Lines

Being one of the most lethal human neoplasms and refractory to such conventional treatment as chemo- and radiotherapy, anaplastic thyroid carcinoma is a prime target for innovative therapy. p53 gene inactivation is a constant feature of this neoplasia. Therefore, we evaluated a therapeutic approach based on an E1B 55-kDa gene-defective adenovirus (ONYX-015) that replicates only in cells with impaired p53 function and leads to cell death. Here we report that the ONYX-015 virus induces cell death in three human thyroid anaplastic carcinoma cell lines (ARO, FRO, and KAT-4). In addition, we found that the growth of xenograft tumors induced in athymic mice by the injection of ARO cells was drastically reduced by ONYX-015 treatment. The ONYX-015 virus worked synergistically with two antineoplastic drugs (doxorubicin and paclitaxel) in inducing ARO and KAT-4 cell death. These results suggest that ONYX-015 may be a valid tool in the treatment of the human thyroid anaplastic carcinoma.

scholarly journals In Vitro Identification and Characterization of CD133pos Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines

PLoS ONE ◽  
2008 ◽  
Vol 3 (10) ◽  
pp. e3544 ◽  
Author(s):  
Giovanni Zito ◽  
Pierina Richiusa ◽  
Alessandra Bommarito ◽  
Elvira Carissimi ◽  
Leonardo Russo ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cell Lines ◽  
Identification And Characterization ◽  
Thyroid Carcinoma Cell

scholarly journals Survivin in relation to Bcl-2, Bax and in situ apoptotic cell death in anaplastic thyroid carcinoma

2011 ◽  
Vol 63 (4) ◽  
pp. 955-963
Author(s):  
Sonja Selemetjev ◽  
Dubravka Cvejic ◽  
Svetlana Savin ◽  
I. Paunovic ◽  
S. Tatic
Keyword(s):  
Cell Death ◽  
Thyroid Carcinoma ◽  
Apoptotic Cell ◽  
Anaplastic Thyroid Carcinoma ◽  
Apoptotic Cell Death ◽  
Staining Score ◽  
Human Malignancy ◽  
Apoptotic Pathways ◽  
Individual Scores

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive human malignancy. It is known that disturbances in apoptotic pathways have a great impact on tumor progression and aggressiveness. In this study the apoptosisrelated molecules Bcl-2 (antiapoptotic), Bax (proapoptotic) and survivin (an inhibitor of apoptosis) were analyzed immunohistochemically in thirty archival cases of ATC. In situ apoptotic cell death was analyzed by the TUNEL method. Mean Bcl-2 staining score (calculated from individual scores from 0-3) was low compared to those for Bax and survivin (p<0.05). High expression of survivin was associated with high Bax expression, and was significantly segregated from high Bcl-2 expressing cases (p<0.05). Despite high Bax expression, apoptotic cell death was low in the investigated carcinomas. In addition, the mean apoptotic index in high survivin expressing carcinomas was significantly lower than in low survivin expressing carcinomas (p<0.05). It could be concluded that down-regulation of Bcl-2 is counterbalanced by up-regulation of survivin, which may overcome the effects of high Bax expression, and, at least partly, explain the low apoptosis rate and high biological aggressiveness of ATC.

scholarly journals BUB1 mediation of caspase-independent mitotic death determines cell fate

2007 ◽  
Vol 178 (2) ◽  
pp. 283-296 ◽  
Author(s):  
Yohei Niikura ◽  
Amruta Dixit ◽  
Ray Scott ◽  
Guy Perkins ◽  
Katsumi Kitagawa
Keyword(s):  
Cell Death ◽  
Cell Fate ◽  
Cell Lines ◽  
Chromosome Instability ◽  
Spindle Checkpoint ◽  
Mitotic Cell ◽  
Endonuclease G ◽  
Colon Tumors ◽  
Mitotic Death ◽  
Apoptosis Inducing Factor

The spindle checkpoint that monitors kinetochore–microtubule attachment has been implicated in tumorigenesis; however, the relation between the spindle checkpoint and cell death remains obscure. In BUB1-deficient (but not MAD2-deficient) cells, conditions that activate the spindle checkpoint (i.e., cold shock or treatment with nocodazole, paclitaxel, or 17-AAG) induced DNA fragmentation during early mitosis. This mitotic cell death was independent of caspase activation; therefore, we named it caspase-independent mitotic death (CIMD). CIMD depends on p73, a homologue of p53, but not on p53. CIMD also depends on apoptosis-inducing factor and endonuclease G, which are effectors of caspase-independent cell death. Treatment with nocodazole, paclitaxel, or 17-AAG induced CIMD in cell lines derived from colon tumors with chromosome instability, but not in cells from colon tumors with microsatellite instability. This result was due to low BUB1 expression in the former cell lines. When BUB1 is completely depleted, aneuploidy rather than CIMD occurs. These results suggest that cells prone to substantial chromosome missegregation might be eliminated via CIMD.

scholarly journals Ionizing radiation results in a mixture of cellular outcomes including mitotic catastrophe, senescence, methuosis, and iron-dependent cell death

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Sandy Adjemian ◽  
Teodora Oltean ◽  
Sofie Martens ◽  
Bartosz Wiernicki ◽  
Vera Goossens ◽  
...  
Keyword(s):  
Cell Death ◽  
Ionizing Radiation ◽  
Cell Lines ◽  
Case Reports ◽  
Cellular Responses ◽  
Mitotic Catastrophe ◽  
High Dose ◽  
X Rays ◽  
Cytotoxic Treatment ◽  
Dependent Cell

AbstractRadiotherapy is commonly used as a cytotoxic treatment of a wide variety of tumors. Interestingly, few case reports underlined its potential to induce immune-mediated abscopal effects, resulting in regression of metastases, distant from the irradiated site. These observations are rare, and apparently depend on the dose used, suggesting that dose-related cellular responses may be involved in the distant immunogenic responses. Ionizing radiation (IR) has been reported to elicit immunogenic apoptosis, necroptosis, mitotic catastrophe, and senescence. In order to link a cellular outcome with a particular dose of irradiation, we performed a systematic study in a panel of cell lines on the cellular responses at different doses of X-rays. Remarkably, we observed that all cell lines tested responded in a similar fashion to IR with characteristics of mitotic catastrophe, senescence, lipid peroxidation, and caspase activity. Iron chelators (but not Ferrostatin-1 or vitamin E) could prevent the formation of lipid peroxides and cell death induced by IR, suggesting a crucial role of iron-dependent cell death during high-dose irradiation. We also show that in K-Ras-mutated cells, IR can induce morphological features reminiscent of methuosis, a cell death modality that has been recently described following H-Ras or K-Ras mutation overexpression.

scholarly journals Mortalin (GRP75/HSPA9) Promotes Survival and Proliferation of Thyroid Carcinoma Cells

2019 ◽  
Vol 20 (9) ◽  
pp. 2069 ◽  
Author(s):  
Dmytro Starenki ◽  
Nadiya Sosonkina ◽  
Seung-Keun Hong ◽  
Ricardo V. Lloyd ◽  
Jong-In Park
Keyword(s):  
Cell Death ◽  
Thyroid Carcinoma ◽  
Thyroid Tumor ◽  
Anaplastic Thyroid Carcinoma ◽  
Mitochondrial Activity ◽  
Phase Arrest ◽  
M Phase ◽  
A Cell ◽  
Mitochondrial Hsp70

We previously reported that upregulation of mortalin (HSPA9/GRP75), the mitochondrial HSP70 chaperone, facilitates tumor cell proliferation and survival in human medullary thyroid carcinoma (MTC), proposing mortalin as a novel therapeutic target for MTC. In this report, we show that mortalin is also upregulated in other thyroid tumor types, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and anaplastic thyroid carcinoma (ATC), and that mortalin depletion can effectively induce growth arrest and cell death in human PTC (TPC-1), FTC (FTC133), and ATC (8505C and C643) cells in culture. Intriguingly, mortalin depletion induced varied effects on cell cycle arrest (G0/G1 phase arrest in TPC-1 and C643, G2/M phase arrest in 8505C, and mild G2/M phase arrest with increased sub-G0/G1 population in FTC133) and on the levels of TP53, E2F-1, p21CIP1, p27KIP1, and poly (ADP-ribose) polymerase cleavage in these cells, suggesting that thyroid tumor cells respond to mortalin depletion in a cell type-specific manner. In these cells, we also determined the efficacy of triphenyl-phosphonium-carboxy-proxyl (Mito-CP) because this mitochondria-targeted metabolism interfering agent exhibited similar tumor suppressive effects as mortalin depletion in MTC cells. Indeed, Mito-CP also induced robust caspase-dependent apoptosis in PTC and ATC cell lines in vitro, exhibiting IC50 lower than PLX4032 in 8505C cells and IC50 lower than vandetanib and cabozantinib in TPC-1 cells. Intriguingly, Mito-CP-induced cell death was partially rescued by mortalin overexpression, suggesting that Mito-CP may inactivate a mechanism that requires mortalin function. These findings support the significance of mortalin and mitochondrial activity in a broad spectrum of thyroid cancer.

scholarly journals Effect of Imatinib Mesylate (Gleevec) on Anaplastic Thyroid Carcinoma Cell Lines 1

2003 ◽  
Vol 88 (10) ◽  
pp. 5043-5044 ◽  
Author(s):  
Constantine S. Mitsiades ◽  
Despoina Sykoutri ◽  
Ciaran McMullan ◽  
Vassiliki Poulaki ◽  
Nicholas Mitsiades
Keyword(s):  
Thyroid Carcinoma ◽  
Imatinib Mesylate ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cell Lines ◽  
Thyroid Carcinoma Cell
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