scholarly journals SIRT6 promotes the Warburg effect of papillary thyroid cancer cell BCPAP through reactive oxygen species

2019 ◽  
Vol Volume 12 ◽  
pp. 2861-2868 ◽  
Author(s):  
Weiping Yu ◽  
Zhou Yang ◽  
Renhong Huang ◽  
Zhijun Min ◽  
Min Ye
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.


Oncotarget ◽  
2015 ◽  
Vol 6 (28) ◽  
pp. 25917-25931 ◽  
Author(s):  
Liping Wang ◽  
Zhufang Tian ◽  
Qi Yang ◽  
Heng Li ◽  
Haixia Guan ◽  
...  

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.


2013 ◽  
Author(s):  
Maqbool Ahmed ◽  
Azhar R. Hussain ◽  
Fouad Al Dayel ◽  
Shahab Uddin ◽  
Khawla S. Al-Kuraya

Author(s):  
Angelica Perna ◽  
Antonio De Luca ◽  
Laura Adelfi ◽  
Tammaro Pasquale ◽  
Bruno Varriale ◽  
...  

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