Sirt3 is a tumor suppressor in lung adenocarcinoma cells

Xiao,Kui; Jiang,Jiehan; Wang,Wei; Cao,Shan; Zhu,Liming; Zeng,Huihui; Ouyang,Ruoyun; Zhou,Rui; Chen,Ping

doi:10.3892/or.2013.2604

Sirt3 is a tumor suppressor in lung adenocarcinoma cells

Authors:
- Kui Xiao
- Jiehan Jiang
- Wei Wang
- Shan Cao
- Liming Zhu
- Huihui Zeng
- Ruoyun Ouyang
- Rui Zhou
- Ping Chen
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Affiliations: Department of Respiratory Medicine, The Second Xiangya Hospital, Institute of Respiratory Disease, Central South University, Changsha, Hunan 410011, P.R. China, Department of Respiratory Medicine, Changsha Central Hospital, Changsha, Hunan 410004, P.R. China, Department of Vascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan 410078, P.R. China, Department of Respiratory Medicine, Hunan Geriatric Hospital, Changsha, Hunan 410016, P.R. China
Published online on: July 8, 2013 https://doi.org/10.3892/or.2013.2604
Pages: 1323-1328

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Abstract

Sirt3, a member of the mammalian sirtuin family protein that is localized to mitochondria, is a NAD+-dependent deacetylase and plays an important role in the control of metabolic activity. Recently, several studies have shown the potential role of Sirt3 in certain types of tumors such as breast cancer and hepatocellular carcinoma. However, the role of Sirt3 in lung adenocarcinoma has never been studied. In the present study, we found that Sirt3 protein expression was downregulated in human lung adenocarcinoma tissue when compared with that in adjacent normal tissue. Overexpression of Sirt3 using adenovirus significantly inhibited the growth of the A549 lung adenocarcinoma cell line. In this cell line, overexpression of Sirt3 induced apoptosis, which was evidenced by Annexin V + PI assay and cleaved caspase-3 immunoblotting. Furthermore, overexpression of Sirt3 increased the bax/bcl-2 and bad/bcl-x/L ratios, and promoted AIF translocation to the nucleus. Finally, Sirt3 overexpression upregulated p53 and p21 protein levels, and decreased intracellular ROS levels. Collectively, our data suggest that Sirt3 is a tumor suppressor in lung adenocarcinoma development and progression and may be a promising therapeutic target for lung adenocarcinoma.

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