scholarly journals ROS-Induced SIRT2 Upregulation Contributes to Cisplatin Sensitivity in Ovarian Cancer

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1137
Author(s):  
Wenyu Wang ◽  
Jihye Im ◽  
Soochi Kim ◽  
Suin Jang ◽  
Youngjin Han ◽  
...  

Cisplatin resistance remains a significant obstacle for improving the clinical outcome of ovarian cancer patients. Recent studies have demonstrated that cisplatin is an important inducer of intracellullar reactive oxygen species (ROS), triggering cancer cell death. Sirtuin 2 (SIRT2), a member of class III NAD+ dependent histone deacetylases (HDACs), has been reported to be involved in regulating cancer hallmarks including drug response. In this study, we aimed to identify the role of SIRT2 in oxidative stress and cisplatin response in cancer. Two ovarian cancer cell lines featuring different sensitivities to cisplatin were used in this study. We found different expression patterns of SIRT2 in cisplatin-sensitive (A2780/S) and cisplatin-resistant (A2780/CP) cancer cells with cisplatin treatment, where SIRT2 expression was augmented only in A2780/S cells. Furthermore, cisplatin-induced ROS generation was responsible for the upregulation of SIRT2 in A2780/S cells, whereas overexpression of SIRT2 significantly enhanced the sensitivity of cisplatin-resistant counterpart cells to cisplatin. Our study proposes that targeting SIRT2 may provide new strategies to potentiate platinum-based chemotherapy in ovarian cancer patients.

2009 ◽  
Vol 114 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Ram Eitan ◽  
Michal Kushnir ◽  
Gila Lithwick-Yanai ◽  
Miriam Ben David ◽  
Moshe Hoshen ◽  
...  

2007 ◽  
Vol 6 (5) ◽  
pp. 795-801 ◽  
Author(s):  
Dineo Khabele ◽  
Deok-Soo Son ◽  
Angelika K. Parl ◽  
Gary L. Goldberg ◽  
Leonard H. Augenlicht ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Li ◽  
Jie Yang ◽  
Ben Yang ◽  
Guoqing Zhao ◽  
Hai Lin ◽  
...  

Ketamine is widely used for cancer pain treatment in clinic, and has been shown to inhibit various tumor cells growth. However, the effect of ketamine on ovarian cancer cells growth and the downstream molecules has not been defined. In the present study, we found that ketamine significantly inhibited the proliferation and survival of six ovarian cancer cell lines. Moreover, ketamine induced ovarian cancer cell cycle arrest, apoptosis, and inhibited colony formation capacity. Since lncRNAs have been identified as key regulators of cancer development, we performed bioinformatics analysis of a GEO dataset and found fourteen significantly altered lncRNAs in ovarian cancer patients. We then investigated the effect of ketamine on these lncRNAs, and found that ketamine regulated the expression of lncRNA PVT1. Mechanistically, ketamine regulated P300-mediated H3K27 acetylation activation in the promoter of PVT1. Our RNA immunoprecipitation experiment indicated that PVT1 bound histone methyltransferase enhancer of zeste homolog 2 (EZH2), and regulated the expression of target gene, including p57, and consequently altered ovarian cancer cell biology. Our study revealed that ketamine could be a potential therapeutic strategy for ovarian cancer patients.


2013 ◽  
Author(s):  
Jin Young Kim ◽  
So Jin Shin ◽  
Keon Uk Park ◽  
Young June Jeon ◽  
Chi Heum Cho ◽  
...  

2019 ◽  
Vol 154 (1) ◽  
pp. 138-143 ◽  
Author(s):  
Federica Tomao ◽  
Lucia Musacchio ◽  
Federica Di Mauro ◽  
Serena Maria Boccia ◽  
Violante Di Donato ◽  
...  

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