Journal
TOXICOLOGY LETTERS
Volume 203, Issue 1, Pages 9-19Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2011.02.013
Keywords
Piperine; MMP-9; PKC alpha; Invasion; Antitumor activity
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Funding
- Chungnam National University
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Piperine is a major component of black pepper, Piper nigrum Linn, used widely in traditional medicine. Several previous studies reported that piperine possesses various beneficial biological activities including antioxidant, anti-tumor and anti-inflammation properties. In the present study, we investigated the inhibitory effects of piperine on tumor invasion and migration and the possible mechanisms involved using human fibrosarcoma HT-1080 cells. We found that piperine suppresses PMA-enhanced matrix metalloproteinase-9 (MMP-9) expression at the protein, mRNA, and transcriptional levels through the suppression of NF-kappa B and AP-1 activation without changing the level of tissue inhibitor of metalloproteinase (TIMP)-1. Piperine also inhibits PMA-enhanced membrane-type 1 MMP expression without changing the level of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Piperine inhibited PMA-induced NF-kappa B and c-Jun nuclear translocation, which are upstream of PMA-induced MMP-9 expression and invasion. Furthermore, piperine strongly repressed the PMA-induced phosphorylation of ERK, which are dependent on the PKC alpha pathway. In conclusion, we demonstrated that the anti-invasive effects of piperine may occur through inhibition of PKC alpha and ERK phosphorylation and reduction of NF-kappa B and AP-1 activation, leading to down-regulation of MMP-9 expression. Thus, piperine has potential as a potent anti-cancer drug in therapeutic strategies for fibrosarcoma metastasis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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