scholarly journals 15-Deoxy-Δ12,14-prostaglandin J2Induces Apoptosis and Upregulates SOCS3 in Human Thyroid Cancer Cells

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Carlos Antônio Trindade-da-Silva ◽  
Carolina Fernandes Reis ◽  
Lara Vecchi ◽  
Marcelo Henrique Napimoga ◽  
Marcelo Sperandio ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Carcinoma Cells ◽  
Human Thyroid ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Natural Ligand ◽  
Thyroid Papillary ◽  
Thyroid Cancer Cells ◽  
Cyclopentenone Prostaglandin ◽  
Different Doses

The cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) is a natural ligand of peroxisome proliferator-activated receptor gamma (PPAR-γ) and a potential mediator of apoptosis in cancer cells. In the present study, we evaluated the effect of 15d-PGJ2in human thyroid papillary carcinoma cells (TPC-1) using different doses of 15d-PGJ2(0.6 to 20 μM) to determine IC50(9.3 μM) via the MTT assay. The supernatant culture medium of the TPC-1 cells that was treated either with 15d-PGJ2or with vehicle (control) for 24 hours was assessed for IL-6 secretion via CBA assay. RT-qPCR was used to evaluate mRNA expression of IL-6, SOCS1, SOCS3, and STAT3. TPC-1 cells treated with 15d-PGJ2decreased the secretion and expression of IL-6 and STAT3, while it increased SOCS1 and SOCS3. Overall, we demonstrated that 15d-PGJ2downregulated IL-6 signaling pathway and led TPC-1 cells into apoptosis. In conclusion, 15d-PGJ2shows the potential to become a new therapeutic approach for thyroid tumors.

scholarly journals Ligands for Peroxisome Proliferator-Activated Receptor γ Inhibit Growth and Induce Apoptosis of Human Papillary Thyroid Carcinoma Cells

2001 ◽  
Vol 86 (5) ◽  
pp. 2170-2177 ◽  
Author(s):  
Kazuyasu Ohta ◽  
Toyoshi Endo ◽  
Kazutaka Haraguchi ◽  
Jerome M. Hershman ◽  
Toshimasa Onaya
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Human Thyroid ◽  
Peroxisome Proliferator ◽  
Papillary Thyroid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Carcinoma Cell Lines

Ligands for peroxisome proliferator-activated receptor γ (PPARγ) induce apoptosis and exert antiproliferative effects on several carcinoma cell lines. The present study investigates the expression of PPARγ and the possibility that agonists for PPARγ also inhibit the growth of human thyroid carcinoma cells. We examined this hypothesis using six cell lines, designated BHP thyroid carcinoma cells, which originated from patients with papillary thyroid carcinoma. RT-PCR analysis revealed that the thyroid carcinoma cell lines BHP2–7, 7–13, 10–3, and 18–21 express PPARγ. More PPARγ was expressed in carcinoma than in adjacent normal thyroid tissue in three of six samples of human papillary carcinoma of the thyroid. PPARγ-positive thyroid carcinoma cells were treated with agonists of PPARγ, troglitazone, BRL 49653, and 15-deoxy-Δ12,14-prostaglandin J2. Troglitazone (10μ mol/L), BRL 49653 (10 μmol/L), and 15-deoxy-Δ12,14-prostaglandin J2 (1 μg/mL) decreased[ 3H]thymidine incorporation and reduced cell number, respectively, in BHP carcinoma cell lines that expressed PPARγ. Under low serum conditions, ligands for PPARγ induced condensation of the nucleus and fragmentation of chromatin into nucleosome ladders. These findings indicate that the death of thyroid carcinoma cells is a form of apoptosis. To investigate the molecular mechanism of the apoptosis, we assessed expression of the apoptosis-regulatory genes bcl-2, bax, and c-myc. Troglitazone significantly increased the expression of c-myc messenger RNA but had no effect on the expression of bcl-2 and bax in thyroid carcinoma cells. These results suggest that, at least in part, the induction of apoptosis in human papillary thyroid carcinoma cells may be due to an increase of c-myc. Troglitazone (500 mg/kg·day) significantly inhibited tumor growth and prevented distant metastasis of BHP18–21 tumors in nude mice in vivo. Taken together, these results suggest that PPARγ agonist inhibit cell growth of some types of human thyroid cancer.

scholarly journals Synergistic Antiproliferative Effects of Combinedγ-Tocotrienol and PPARγAntagonist Treatment Are Mediated through PPARγ-Independent Mechanisms in Breast Cancer Cells

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Abhita Malaviya ◽  
Paul W. Sylvester
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Combined Treatment ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Antiproliferative Effects ◽  
Natural Ligand ◽  
Anticancer Effects ◽  
Cox 2

Previous findings showed that the anticancer effects of combinedγ-tocotrienol and peroxisome proliferator activated receptorγ(PPARγ) antagonist treatment caused a large reduction in PPARγexpression. However, other studies suggest that the antiproliferative effects ofγ-tocotrienol and/or PPARγantagonists are mediated, at least in part, through PPARγ-independent mechanism(s). Studies were conducted to characterize the role of PPARγin mediating the effects of combined treatment ofγ-tocotrienol with PPARγagonists or antagonists on the growth of PPARγnegative +SA mammary cells and PPARγ-positive and PPARγ-silenced MCF-7 and MDA-MB-231 breast cancer cells. Combined treatment ofγ-tocotrienol with PPARγantagonist decreased, while combined treatment ofγ-tocotrienol with PPARγagonist increased, growth of all cancer cells. However, treatment with high doses of 15d-PGJ2, an endogenous natural ligand for PPARγ, had no effect on cancer cell growth. Western blot and qRT-PCR studies showed that the growth inhibitory effects of combinedγ-tocotrienol and PPARγantagonist treatment decreased cyclooxygenase (COX-2), prostaglandin synthase (PGDS), and prostaglandin D2(PGD2) synthesis. In conclusion, the anticancer effects of combinedγ-tocotrienol and PPARγantagonists treatment in PPARγnegative/silenced breast cancer cells are mediated through PPARγ-independent mechanisms that are associated with a downregulation in COX-2, PGDS, and PGD2synthesis.

Anti-proliferative effects of evodiamine on human thyroid cancer cells

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

scholarly journals Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space

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.

scholarly journals Activation of Peroxisome Proliferator-activated Receptor α (PPARα) Suppresses Hypoxia-inducible Factor-1α (HIF-1α) Signaling in Cancer Cells

2012 ◽  
Vol 287 (42) ◽  
pp. 35161-35169 ◽  
Author(s):  
Jundong Zhou ◽  
Shuyu Zhang ◽  
Jing Xue ◽  
Jori Avery ◽  
Jinchang Wu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Proteasome Inhibitors ◽  
Tube Formation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hypoxia Inducible Factor 1Α ◽  
Anticancer Properties ◽  
Pparγ Agonist ◽  
Expression And Activity

Activation of peroxisome proliferator-activated receptor α (PPARα) has been demonstrated to inhibit tumor growth and angiogenesis, yet the mechanisms behind these actions remain to be characterized. In this study, we examined the effects of PPARα activation on the hypoxia-inducible factor-1α (HIF-1α) signaling pathway in human breast (MCF-7) and ovarian (A2780) cancer cells under hypoxia. Incubation of cancer cells under 1% oxygen for 16 h significantly induced HIF-1α expression and activity as assayed by Western blotting and reporter gene analysis. Treatment of the cells with PPARα agonists, but not a PPARγ agonist, prior to hypoxia diminished hypoxia-induced HIF-1α expression and activity, and addition of a PPARα antagonist attenuated the suppression of HIF-1α signaling. Activation of PPARα attenuated hypoxia-induced HA-tagged HIF-1α protein expression without affecting the HA-tagged HIF-1α mutant protein level, indicating that PPARα activation promotes HIF-1α degradation in these cells. This was further confirmed using proteasome inhibitors, which reversed PPARα-mediated suppression of HIF-1α expression under hypoxia. Using the co-immunoprecipitation technique, we found that activation of PPARα enhances the binding of HIF-1α to von Hippel-Lindau tumor suppressor (pVHL), a protein known to mediate HIF-1α degradation through the ubiquitin-proteasome pathway. Following PPARα-mediated suppression of HIF-1α signaling, VEGF secretion from the cancer cells was significantly reduced, and tube formation by endothelial cells was dramatically impaired. Taken together, these findings demonstrate for the first time that activation of PPARα suppresses hypoxia-induced HIF-1α signaling in cancer cells, providing novel insight into the anticancer properties of PPARα agonists.

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