Abstract |
Νuclear factor-κB (NF-κB) and activator protein-1 (AP-1) are major transcription factors that have been associated with breast cancer metastasis by inducing matrix metalloproteinase-9 (MMP-9) expression. In this study, we investigated the inhibitory effects of guggulsterone isomers (cis or trans) on 12-O-tetradecanoylpho-bol-13-acetate (TPA)-induced MMP-9 expression. Cis- guggulsterone inhibited TPA-induced MMP expression by blocking IκB kinase (IKK)/NF-κB signaling, whereas trans- guggulsterone blocked mitogen-activated protein kinase (MAPK)/AP-1 signaling. Cis- guggulsterone was more potent than trans- guggulsterone in the inhibition of TPA-induced MMP-9 expression and invasion of MCF-7 cells. Furthermore, we found that the combination of these isomers exerted an additive effect on the inhibition of MCF-7 cell invasion. These results suggest that guggulsterone isomers downregulate MMP-9 expression and tumor cell invasion through the isomer-specific suppression of IKK/NF-κB and MAPK/AP-1 activation. In addition, the suppression of MMP-9 expression correlated well with the inhibition of cell invasion.
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Authors | Eun-Mi Noh, Eun Yong Chung, Hyun Jo Youn, Sung Hoo Jung, Hyun Hur, Young-Rae Lee, Jong-Suk Kim |
Journal | International journal of molecular medicine
(Int J Mol Med)
Vol. 31
Issue 2
Pg. 393-9
(Feb 2013)
ISSN: 1791-244X [Electronic] Greece |
PMID | 23242121
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- NF-kappa B
- Pregnenediones
- Transcription Factor AP-1
- pregna-4,17-diene-3,16-dione
- I-kappa B Kinase
- Mitogen-Activated Protein Kinases
- Matrix Metalloproteinase 9
- Tetradecanoylphorbol Acetate
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Topics |
- Antineoplastic Agents, Phytogenic
(chemistry, pharmacology)
- Breast
(drug effects, metabolism, pathology)
- Breast Neoplasms
(drug therapy, metabolism, pathology)
- Cell Survival
(drug effects)
- Commiphora
(chemistry)
- Female
- Humans
- I-kappa B Kinase
(antagonists & inhibitors, metabolism)
- Isomerism
- MCF-7 Cells
- Matrix Metalloproteinase 9
(genetics)
- Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism)
- NF-kappa B
(antagonists & inhibitors, metabolism)
- Neoplasm Invasiveness
(prevention & control)
- Pregnenediones
(chemistry, pharmacology)
- Signal Transduction
(drug effects)
- Tetradecanoylphorbol Acetate
(pharmacology)
- Transcription Factor AP-1
(antagonists & inhibitors, metabolism)
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