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Molecules 2014, 19(5), 6047-6057; doi:10.3390/molecules19056047
Article

Bufalin Alters Gene Expressions Associated DNA Damage, Cell Cycle, and Apoptosis in Human Lung Cancer NCI-H460 Cells in Vitro

1,2, 3, 4, 3, 3, 5,6, 7, 6,8,*  and 3,9,*
Received: 12 March 2014; in revised form: 2 May 2014 / Accepted: 8 May 2014 / Published: 13 May 2014
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Abstract: Lung cancer is the leading cause of cancer related death and there is no effective treatment to date. Bufalin has been shown effective in inducing apoptosis and DNA damage in lung cancer cells. However, the genetic mechanisms underlying these actions have not been elucidated yet. Cultured NCI-H460 cells were treated with or without 2 μM of bufalin for 24 h. The total RNA was extracted from each treatment for cDNA synthesis and labeling, microarray hybridization, and then followed by flour-labeled cDNA hybridized on chip. The localized concentrations of fluorescent molecules were detected and quantitated and analyzed by Expression Console software (Affymetrix) with default RMA parameters. The key genes involved and their possible interaction pathways were mapped by GeneGo software. About 165 apoptosis-related genes were affected. CASP9 was up-regulated by 5.51 fold and THAP1 by 2.75-fold while CCAR1 was down-regulated by 2.24 fold. 107 genes related to DNA damage/repair were affected. MDC1 was down-regulated by 2.22-fold, DDIT4 by 2.52 fold while GADD45B up-regulated by 3.72 fold. 201 genes related to cell cycles were affected. CCPG1 was down-regulated by 2.11 fold and CDCA7L by 2.71 fold. Many genes about apoptosis, cell cycle regulation and DNA repair are changed significantly following bufalin treatment in NCI-H460 cells. These changes provide an in depth understanding of cytotoxic mechanism of bufalin in genetic level and also offer many potentially useful biomarkers for diagnosis and treatment of lung cancer in future.
Keywords: bufalin; cDNA microarray; DNA damage; cell cycle; apoptosis; NCI-H460 cells bufalin; cDNA microarray; DNA damage; cell cycle; apoptosis; NCI-H460 cells
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

Wu, S.-H.; Hsiao, Y.-T.; Chen, J.-C.; Lin, J.-H.; Hsu, S.-C.; Hsia, T.-C.; Yang, S.-T.; Hsu, W.-H.; Chung, J.-G. Bufalin Alters Gene Expressions Associated DNA Damage, Cell Cycle, and Apoptosis in Human Lung Cancer NCI-H460 Cells in Vitro. Molecules 2014, 19, 6047-6057.

AMA Style

Wu S-H, Hsiao Y-T, Chen J-C, Lin J-H, Hsu S-C, Hsia T-C, Yang S-T, Hsu W-H, Chung J-G. Bufalin Alters Gene Expressions Associated DNA Damage, Cell Cycle, and Apoptosis in Human Lung Cancer NCI-H460 Cells in Vitro. Molecules. 2014; 19(5):6047-6057.

Chicago/Turabian Style

Wu, Shin-Hwar; Hsiao, Yung-Ting; Chen, Jaw-Chyum; Lin, Ju-Hwa; Hsu, Shu-Chun; Hsia, Te-Chun; Yang, Su-Tso; Hsu, Wu-Huei; Chung, Jing-Gung. 2014. "Bufalin Alters Gene Expressions Associated DNA Damage, Cell Cycle, and Apoptosis in Human Lung Cancer NCI-H460 Cells in Vitro." Molecules 19, no. 5: 6047-6057.


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