cDNA microarray analysis of the effect of cantharidin on DNA damage, cell cycle and apoptosis-associated gene expression in NCI-H460 human lung cancer cells in vitro.

Abstract	Cantharidin (CTD) induces cytotoxic effects in different types of human cancer cell; however, to date, there have been no studies on the effects of CTD on gene expression in human lung cancer cells and the potential associated signaling pathways. Therefore, the present study aimed to investigate how CTD affects the expression of key genes and functional pathways of human H460 lung cancer cells using complementary DNA microarray analysis. Human H460 lung cancer cells were cultured for 24 h in the presence or absence of 10 µM CTD; gene expression was then examined using microarray analysis. The results indicated that 8 genes were upregulated > 4-fold, 29 genes were upregulated >3-4-fold and 156 genes were upregulated >2-3-fold. In addition, 1 gene was downregulated >4 fold, 14 genes were downregulated >3-4-fold and 150 genes were downregulated >2-3 fold in H460 cells following exposure to CTD. It was found that CTD affected DNA damage genes, including DNIT3 and GADD45A, which were upregulated 2.26- and 2.60-fold, respectively, as well as DdiT4, which was downregulated 3.14-fold. In addition, the expression of genes associated with the cell cycle progression were altered, including CCND2, CDKL3 and RASA4, which were upregulated 2.72-, 2.19- and 2.72-fold, respectively; however, CDC42EP3 was downregulated 2.16-fold. Furthermore, apoptosis-associated genes were differentially expressed, including CARD6, which was upregulated 3.54-fold. In conclusion, the present study demonstrated that CTD affected the expression of genes associated with DNA damage, cell cycle progression and apoptotic cell death in human lung cancer H460 cells.
Authors	Te-Chun Hsia, Chien-Chih Yu, Shu-Chun Hsu, Nou-Ying Tang, Hsu-Feng Lu, Chun-Shu Yu, Shin-Hwar Wu, Jaung-Geng Lin, Jing-Gung Chung
Journal	Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 1 Pg. 1030-42 (Jul 2015) ISSN: 1791-3004 [Electronic] Greece
PMID	25815777 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents CCND2 protein, human Cell Cycle Proteins Cyclin D2 DDIT4 protein, human Enzyme Inhibitors GADD45A protein, human Nuclear Proteins RASA4 protein, human Transcription Factors ras GTPase-Activating Proteins CDKL3 protein, human Protein Serine-Threonine Kinases Cantharidin
Topics	Antineoplastic Agents (pharmacology) Apoptosis (drug effects) Cantharidin (pharmacology) Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology) Cell Cycle (drug effects) Cell Cycle Proteins (genetics, metabolism) Cell Line, Tumor Cyclin D2 (genetics, metabolism) DNA Damage Enzyme Inhibitors (pharmacology) Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Ontology Humans Microarray Analysis Molecular Sequence Annotation Nuclear Proteins (genetics, metabolism) Oligonucleotide Array Sequence Analysis Protein Serine-Threonine Kinases (genetics, metabolism) Signal Transduction Transcription Factors (genetics, metabolism) ras GTPase-Activating Proteins (genetics, metabolism)

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