title: 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: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors: Te-Chun
authors: TC
authors: Hsia
authors: School of Pharmacy, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors: Chien-Chih
authors: CC
authors: Yu
authors: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors: Shu-Chun
authors: SC
authors: Hsu
authors: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors: Nou-Ying
authors: NY
authors: Tang
authors: Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei 11220, Taiwan, R.O.C.
authors: Hsu-Feng
authors: HF
authors: Lu
authors: School of Pharmacy, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors: Chun-Shu
authors: CS
authors: Yu
authors: Division of Critical Care Medicine, Department of Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C.
authors: Shin-Hwar
authors: SH
authors: Wu
authors: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors: Jaung-Geng
authors: JG
authors: Lin
authors: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002193:Cantharidin / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D006801:Humans; D046228:Microarray Analysis; D058977:Molecular Sequence Annotation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D000970:Antineoplastic Agents; D002193:Cantharidin; D018797:Cell Cycle Proteins; D056742:Cyclin D2; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D020703:ras GTPase-Activating Proteins; C080336:CCND2 protein, human; C469991:DDIT4 protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C491144:RASA4 protein, human; C477873:CDKL3 protein, human