Int. J. Mol. Sci. 2013, 14(3), 5806-5816; doi:10.3390/ijms14035806
Article

Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D-Cdk4 Expression in Non-Small Cell Lung Cancer (NSCLC)

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 and 4,7,*
Received: 23 October 2012; in revised form: 17 January 2013 / Accepted: 17 January 2013 / Published: 12 March 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract: Lung cancer is the most common cause of cancer-related death. Nonetheless, a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents. In recent studies, Simvastatin (SIM) has demonstrated anti-tumor activity, as well as potent chemopreventive action. As an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), SIM has been shown to stimulate apoptotic cell death. In this study, an MTT assay revealed the cytotoxic activity of SIM against human large cell lung cancer (Non-small cell lung cancer; NSCLC) cells (NCI-H460); however, induced apoptosis was not observed in NCI-H460 cells. Protein expression levels of cell cycle regulating proteins Cdk4, Cyclin D1, p16 and p27 were markedly altered by SIM. Collectively, our results indicate that SIM inhibits cell proliferation and arrests NCI-H460 cell cycle progression via inhibition of cyclin-dependent kinases and cyclins and the enhancement of CDK inhibitors p16 and p27. Our findings suggest that, in addition to the known effects on hypercholesterolemia therapy, SIM may also provide antitumor activity in established NSCLC.
Keywords: simvastatin; non-small cell lung cancer; cell cycle arrest; CyclinD-Cdk4
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.

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MDPI and ACS Style

Liang, Y.-W.; Chang, C.-C.; Hung, C.-M.; Chen, T.-Y.; Huang, T.-Y.; Hsu, Y.-C. Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D-Cdk4 Expression in Non-Small Cell Lung Cancer (NSCLC). Int. J. Mol. Sci. 2013, 14, 5806-5816.

AMA Style

Liang Y-W, Chang C-C, Hung C-M, Chen T-Y, Huang T-Y, Hsu Y-C. Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D-Cdk4 Expression in Non-Small Cell Lung Cancer (NSCLC). International Journal of Molecular Sciences. 2013; 14(3):5806-5816.

Chicago/Turabian Style

Liang, Yu-Wei; Chang, Chi-Chang; Hung, Chao-Ming; Chen, Tzu-Yu; Huang, Tzuu-Yuan; Hsu, Yi-Chiang. 2013. "Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D-Cdk4 Expression in Non-Small Cell Lung Cancer (NSCLC)." Int. J. Mol. Sci. 14, no. 3: 5806-5816.


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