Pipoxolan inhibits CL1-5 lung cancer cells migration and invasion through inhibition of MMP-9 and MMP-2

  • Chem Biol Interact. 2015 Jul 5:236:19-30. doi: 10.1016/j.cbi.2015.04.012.
Min-Min Lee  1 ,  Ying-Yi Chen  2 ,  Pei-Yi Liu  3 ,  Stephen Hsu  4 ,  Ming-Jyh Sheu  5
Affiliations
  • 1. Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
  • 2. School of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
  • 3. 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.
  • 4. Department of Physical Therapy, College of Health Care, China Medical University, Taichung 40402, Taiwan.
  • 5. School of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan. Electronic address: [email protected].
PMID: 25899827 DOI: 10.1016/j.cbi.2015.04.012
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.

Keywords
CL1–5; JNK1/2; Matrix metalloproteinase; Migration; Pipoxolan; p38.
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