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

Molecules

Shin-Hwar Wu¹  Yung-Ting Hsiao²  Jaw-Chyum Chen⁵  Ju-Hwa Lin²  Shu-Chun Hsu²  Te-Chun Hsia⁶  Su-Tso Yang³  Wu-Huei Hsu⁴ 

[1]Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan

[2]Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan

[3]Department of Radiology, China Medical University Hospital, Taichung 40447, Taiwan

[4]Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan

[5]Department of Medicinal Botany and Health Applications, Da-Yeh University, Changhua 51591, Taiwan

[6]Gradualted Institute of Chinese Medical Science, China Medical University, Taichung 40402, Taiwan

关键词: bufalin;    cDNA microarray;    DNA damage;    cell cycle;    apoptosis;    NCI-H460 cells;   

DOI  :  10.3390/molecules19056047

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.