title: Pipoxolan inhibits CL1-5 lung cancer cells migration and invasion through inhibition of MMP-9 and MMP-2.
abstract: Pipoxolan has been reported to have antitumor activity. However, the effects of pipoxolan on lung cancer cell metastasis remains unclear. This study examined the anti-metastatic effects of pipoxolan on lung adenocarcinoma cancer cells (i.e. CL1-5, CL1-0, and A549) and its underlying molecular mechanisms. Firstly, CL1-5 cell migration was markedly suppressed by pipoxolan when examined by wound scratch assay. Furthermore, transwell and matrigel invasion assays revealed that pipoxolan inhibited lung cancer cells (i.e. CL1-5, CL1-0, and A549) migration/invasion, and showed more sensitive to CL1-5 cell. Therefore, the anti-metastatic effects from pipoxolan have been focused on CL1-5 lung cancer cells. Secondly, these observations have been associated with the reduction in the activities and expressions of matrix metalloproteinase (MMP)-2 and -9 in CL1-5 lung cancer cells. Lastly, pipoxolan administration significantly inhibited phosphorylation c-Jun N-terminal kinase (p-JNK), and p38 MAP Kinase (MAPK) of CL1-5 cells. Based on these results, our results showed that management CL1-5 cells with pipoxolan down-regulated phosphorylation JNK and p38, and then, MMP-2 and -9. These results suggest that pipoxolan might have a new therapeutic potential for anti-metastatic effects in lung cancer cells.
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Lee
authors.affiliation: School of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Chen
authors.affiliation: School of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan; Department of Pharmacy, Far Eastern Memorial Hospital, Banciao District, New Taipei City 220, Taiwan.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Liu
authors.affiliation: Department of Physical Therapy, College of Health Care, China Medical University, Taichung 40402, Taiwan.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hsu
authors.affiliation: School of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan. Electronic address: soybean13mtdtw@gmail.com.
authors.forename: Ming-Jyh
authors.initials: MJ
authors.lastname: Sheu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004148:Dioxolanes / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004148:Dioxolanes; D061965:Matrix Metalloproteinase Inhibitors; C000121:pipoxolan; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: CL1–5; JNK1/2; Matrix metalloproteinase; Migration; Pipoxolan; p38