title: Cantharidin induces DNA damage and inhibits DNA repair-associated protein levels in NCI-H460 human lung cancer cells.
abstract: Cantharidin is one of the major compounds from mylabris and it has cytotoxic effects in many different types of human cancer cells. Previously, we found that cantharidin induced cell death through cell cycle arrest and apoptosis induction in human lung cancer NCI-H460 cells. However, cantharidin-affected DNA damage, repair, and associated protein levels in NCI-H460 cells have not been examined. In this study, we determined whether cantharidin induced DNA damage and condensation and altered levels of proteins in NCI-H460 cells in vitro. Incubation of NCI-H460 cells with 0, 2.5, 5, 10, and 15 μM of cantharidin caused a longer DNA migration smear (comet tail). Cantharidin also increased DNA condensation. These effects were dose-dependent. Cantharidin (5, 10, and 15 μM) treatment of NCI-H460 cells reduced protein levels of ataxia telangiectasia mutated (ATM), breast cancer 1, early onset (BRCA-1), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK), O(6) -methylguanine-DNA methyltransferase (MGMT), and mediator of DNA damage checkpoint protein 1 (MDC1). Protein translocation of p-p53, p-H2A.X (S140), and MDC1 from cytoplasm to nucleus was induced by cantharidin in NCI-H460 cells. Taken together, this study showed that cantharidin caused DNA damage and inhibited levels of DNA repair-associated proteins. These effects may contribute to cantharidin-induced cell death in vitro.
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.|Department of Internal Medicine, China Medical University Hospital, Taichung, 404, Taiwan.
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
authors.forename: Ju-Hwa
authors.initials: JH
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
authors.forename: Nou-Ying
authors.initials: NY
authors.lastname: Tang
authors.affiliation: Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, 112, Taiwan.
authors.forename: Hsu-Feng
authors.initials: HF
authors.lastname: Lu
authors.affiliation: Division of Critical Care Medicine, Department of Medicine, Changhua Christian Hospital, Changhua, 500, Taiwan.
authors.forename: Shin-Hwar
authors.initials: SH
authors.lastname: Wu
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
authors.forename: Jaung-Geng
authors.initials: JG
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.|Department of Biotechnology, Asia University, Wufeng, Taichung, 413, Taiwan.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002193:Cantharidin / Q000633:toxicity*; D045744:Cell Line, Tumor; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D045643:DNA Repair Enzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal
chemical_list: D045643:DNA Repair Enzymes; D002193:Cantharidin
keywords: DNA damage; DNA repair; cantharidin; comet assay; human lung cancer NCI-H460 cells