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The Scientific World Journal
Volume 2014, Article ID 937051, 8 pages
Research Article

The Antiproliferative and Apoptotic Effects of Sirtinol, a Sirtuin Inhibitor on Human Lung Cancer Cells by Modulating Akt/β-Catenin-Foxo3A Axis

1Department of Thoracic Surgery, Chi-Mei Medical Center, Tainan 710, Taiwan
2Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan
3Department of Biological Sciences, National Sun Yat-sen University, 70 Lien Hai Road, Kaohsiung 804, Taiwan
4Department of Fragrance and Cosmetics Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6Department of Biological Sciences and Technology, National University of Tainan, Tainan 700, Taiwan
7Translational Research Center, Cancer Center, Department of Medical Research, and Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Received 18 June 2014; Revised 29 June 2014; Accepted 30 June 2014; Published 12 August 2014

Academic Editor: Li-Yeh Chuang

Copyright © 2014 Yao Fong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Sirtuins, NAD+-dependent deacetylases, could target both histones and nonhistone proteins in mammalian cells. Sirt1 is the major sirtuin and has been shown to involve various cellular processes, including antiapoptosis, cellular senescence. Sirt1 was reported to be overexpressed in many cancers, including lung cancer. Sirtinol, a specific inhibitor of Sirt1, has been shown to induce apoptosis of cancer cells by elevating endogenous level of reactive oxygen species. In the study, we investigated the effect of sirtinol on the proliferation and apoptosis of nonsmall cell lung cancer (NSCLC) H1299 cells. The results of proliferation assay and colony formation assay showed the antigrowth effect of sirtinol. The annexin-V staining further confirmed the apoptosis induction by sirtinol treatment. Interestingly, the levels of phosphorylated Akt and β-catenin were significantly downregulated with treating the apoptotic inducing doses. On the contrary, sirtinol treatment causes the significantly increased level of FoxO3a, a proapoptotic transcription factor targeted by Sirt1. These above results suggested that sirtinol may inhibit cell proliferation of H1299 cells by regulating the axis of Akt-β-catenin-FoxO3a. Overall, this study demonstrates that sirtinol attenuates the proliferation and induces apoptosis of NSCLC cells, indicating the potential treatment against NSCLC cells by inhibiting Sirt1 in future applications.