scholarly journals Regulatory role of estrogen-induced reactive oxygen species in the modulatory function of UCP 2 in papillary thyroid cancer cells

IUBMB Life ◽  
2015 ◽  
Vol 67 (11) ◽  
pp. 837-846 ◽  
Author(s):  
Sithul Hima ◽  
Sreeharshan Sreeja
Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1229
Author(s):  
Abdul Q. Khan ◽  
Elham A. N. Mohamed ◽  
Ishrat Hakeem ◽  
Aneeza Nazeer ◽  
Shilpa Kuttikrishnan ◽  
...  

Sanguinarine (SNG), a natural compound with an array of pharmacological activities, has promising therapeutic potential against a number of pathological conditions, including malignancies. In the present study, we have investigated the antiproliferative potential of SNG against two well-characterized papillary thyroid cancer (PTC) cell lines, BCPAP and TPC-1. SNG significantly inhibited cell proliferation of PTC cells in a dose and time-dependent manner. Western blot analysis revealed that SNG markedly attenuated deregulated expression of p-STAT3, without affecting total STAT3, and inhibited growth of PTC via activation of apoptotic and autophagy signaling cascade, as SNG treatment of PTC cells led to the activation of caspase-3 and caspase-8; cleavage of PARP and activation of autophagy markers. Further, SNG-mediated anticancer effects in PTC cells involved the generation of reactive oxygen species (ROS) as N-acetyl cysteine (NAC), an inhibitor of ROS, prevented SNG-mediated antiproliferative, apoptosis and autophagy inducing action. Interestingly, SNG also sensitized PTC cells to chemotherapeutic drug cisplatin, which was inhibited by NAC. Finally, SNG suppressed the growth of PTC thyrospheres and downregulated stemness markers ALDH2 and SOX2. Altogether, the findings of the current study suggest that SNG has anticancer potential against PTC cells as well its derived cancer stem-like cells, most likely via inactivation of STAT3 and its associated signaling molecules.


2020 ◽  
Author(s):  
Zhou Yang ◽  
Renhong Huang ◽  
Weiping Yu ◽  
Zhijun Min ◽  
Min Ye

Abstract Background: Our previous study has demonstrated SIRT6 promotes aggression and epithelial-mesenchymal transition (EMT) in papillary thyroid cancer (PTC). In this study, we focused on the regulatory axis between SIRT6-Autophagy-Warburg effect.Methods: Autophagy activation was confirmed by Western Blotting, quantitative PCR, immunofluorescence and transmission electron microscopy. Warburg effect was examined by Seahorse XF96 analysis and PET imaging. Regulation of SIRT6 in negatively regulates reactive oxygen species (NRROS) was confirmed by chromatin immunoprecipitation.Results: We innovatively confirmed overexpression of SIRT6 depleted histone H3 lysine 56 acetylation (H3K56ac) of NRROS in vitro, thus increased reactive oxygen species (ROS). Then, accumulated ROS activated endoplasmic reticulum stress (ER stress), and subsequently induced autophagy. Furthermore, the overexpression of SIRT6 inhibited Glucose Transporter 1 (Glut1) via autophagic degradation, thus ulteriorly suppressed Warburg effect. Treatment of ROS scavenger N-acetyl-L-cysteine (NAC, 5mM) or autophagy inhibitor chloroquine (CQ) both rescued the inhibition of Warburg effect. In addition, higher concentration of NAC (15mM) deepened the inhibited Warburg effect. This concentration-dependent bilateral effects of NAC in this process had been confirmed owe to regulation of AMPK signaling pathway. Finally, we further determined above mechanism in vivo via subcutaneous xenografts in nude mice applied with 18F-FDG PET/CT.Conclusions: We identified a SIRT6-ROS-ERstress-Autophagy-Glut1-Warburg effect axis in PTC, which may provide new target for therapy. In addition, NAC (low concentration) and CQ which previously been considered as tumor inhibitors, have been shown to promote tumorigenesis in PTC with high SIRT6 expression via activation of Warburg effect.


Author(s):  
Saverio M. Lepore ◽  
Valentina Maggisano ◽  
Giovanni E. Lombardo ◽  
Jessica Maiuolo ◽  
Vincenzo Mollace ◽  
...  

Background: The sesquiterpene lactone cynaropicrin, a major constituent of the artichoke leaves extracts, has shown several biologic activities in many preclinical experimental models, including anti-proliferative effects. Objective: Herein we evaluated the effects of cynaropicrin on the growth of three human anaplastic thyroid carcinoma cell lines, investigating the molecular mechanism underlying its action. Method: MTT assay was used to evaluate the viability of CAL-62, 8505C and SW1736 cells, and flow cytometry to analyse cell cycle distribution. Western blot was performed to detect the levels of STAT3 phosphorylation and NFkB activation. Antioxidant effects were analyzed by measuring the reactive oxygen species and malonyldialdehyde dosage was used to check the presence of lipid peroxidation. Results: Viability of CAL-62, 8505C and SW1736 cells was significantly reduced by cynaropicrin in a dose- and time-dependent way, with an EC50 of about 5 µM observed after 48 h of treatment with the compound. Cellular growth inhibition was accompanied both by an arrest of the cell cycle, mainly in the G2/M phase, and the presence of a significant percentage of necrotic cells. After 48 h of treatment with 10 µM of cynaropicrin, a reduced nuclear expression of NFkB and STAT3 phosphorylation were also revealed. Moreover, we observed an increase in lipid peroxidation, without any significant effect on the reactive oxygen species production. Conclusion: These results demonstrate that cynaropicrin reduces the viability and promotes cytotoxic effects in anaplastic thyroid cancer cells associated with reduced NFkB expression, STAT3 phosphorylation and increased lipid peroxidation. Further characterization of the properties of this natural compound may open the way for using cynaropicrin as an adjuvant in the treatment of thyroid cancer.


RSC Advances ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 4163-4163
Author(s):  
Laura Fisher

Retraction of ‘Overexpression of PCDH8 inhibits proliferation and invasion, and induces apoptosis in papillary thyroid cancer cells’ by Liang Chang et al., RSC Adv., 2018, 8, 18030–18037, DOI: 10.1039/C8RA02291G.


2009 ◽  
Vol 379 (2) ◽  
pp. 626-631 ◽  
Author(s):  
Chi-Iou Lin ◽  
Edward E. Whang ◽  
Michael A. Abramson ◽  
David B. Donner ◽  
Monica M. Bertagnolli ◽  
...  

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Hai Li ◽  
Hongyu Guan ◽  
Yan Guo ◽  
Weiwei Liang ◽  
Liehua Liu ◽  
...  

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