title: Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways.
abstract: Cantharidin (CTD), a component of natural mylabris (Mylabris phalerata Pallas), has been shown to have biological activities and induce cell death in many human cancer cells. In the present study, we investigated the effect of CTD on cell migration and invasion of NCI-H460 human lung cancer cells. Cell viability was examined and results indicated that CTD decreased the percentage of viable cells in dose-dependent manners. CTD inhibited cell migration and invasion in dose-dependent manners. Gelatin zymography analysis was used to measure the activities of matrix metalloproteinases (MMP-2/-9) and the results indicated that CTD inhibited the enzymatic activities of MMP-2/-9 of NCI-H460 cells. Western blotting was used to examine the protein expression of NCI-H460 cells after incubation with CTD and the results showed that CTD decreased the expression of MMP-2/-9, focal adhesion kinase (FAK), Ras homolog gene family, member A (Rho A), phospho-protein kinase B (AKT) (Thr308)(p-AKT(308)), phospho-extracellular signal-regulated kinase1/2 (p-ERK1/2), phospho-p38 mitogen-activated protein (MAP) kinase (p-p38), phospho c-Jun N-terminal kinase 1/2 (p-JNK1/2), nuclear factor-κB (NF-κB) and urokinase plasminogen activator (UPA). Furthermore, confocal laser microscopy was used to confirm that CTD suppressed the expression of NF-κB p65, but did not significantly affect protein kinase C (PKC) translocation in NCI-H460 cells. Based on those observations, we suggest that CTD may be used as a novel anticancer metastasis agent for lung cancer in the future.
authors: Department of Respiratory Therapy, School of Health, China Medical University, Taichung, Taiwan, R.O.C.|Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors: Te-Chun
authors: TC
authors: Hsia
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors: Chien-Chih
authors: CC
authors: Yu
authors: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
authors: Yung-Ting
authors: YT
authors: Hsiao
authors: Division of Critical Care Medicine, Department of Medicine, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
authors: Shin-Hwar
authors: SH
authors: Wu
authors: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors: DA-Tian
authors: DT
authors: Bau
authors: Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan, R.O.C.
authors: Hsu-Feng
authors: HF
authors: Lu
authors: Department of Physiology, China Medical University, Taichung, Taiwan, R.O.C.
authors: Yi-Ping
authors: YP
authors: Huang
authors: Department of Respiratory Therapy, School of Health, China Medical University, Taichung, Taiwan, R.O.C.
authors: Jaung-Geng
authors: JG
authors: Lin
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw sjchang@mail.cmu.edu.tw.
authors: Shu-Jen
authors: SJ
authors: Chang
authors: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw sjchang@mail.cmu.edu.tw.|Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan, R.O.C.
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D002193:Cantharidin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D014568:Urokinase-Type Plasminogen Activator; D002193:Cantharidin
keywords: Cantharidin; NCI-H460 cells; UPA; invasion; migration