Antroquinonol from Antrodia Camphorata suppresses breast tumor migration/invasion through inhibiting ERK-AP-1- and AKT-NF-κB-dependent MMP-9 and epithelial-mesenchymal transition expressions
| Autor: | Ku-Chung Chen, Chia Hsiung Cheng, Wai-Theng Lee, Yen-Chou Chen, Tzong-Huei Lee, Cheng Wei Lin |
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| Rok vydání: | 2014 |
| Předmět: |
MAPK/ERK pathway
Epithelial-Mesenchymal Transition Cell Survival Ubiquinone Down-Regulation Breast Neoplasms Toxicology chemistry.chemical_compound Cell Movement Cell Line Tumor Gene expression Humans Epithelial–mesenchymal transition Antrodia Phosphorylation Protein kinase B PI3K/AKT/mTOR pathway Mitogen-Activated Protein Kinase 3 biology NF-kappa B NF-κB General Medicine biology.organism_classification Transcription Factor AP-1 chemistry Matrix Metalloproteinase 9 Cancer research MCF-7 Cells Tetradecanoylphorbol Acetate Food Science Signal Transduction |
| Zdroj: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 78 |
| ISSN: | 1873-6351 |
| Popis: | Antroquinonol (ANQ) is an ubiquinon derivative isolated from the mycelium of Antrodia camphorata. However, the effect of ANQ on breast cancer treatment is unknown. We found that ANQ significantly suppressed the migration and invasion of breast cancer MDA-MB-231 cells, and inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasiveness by MCF7 cells. ANQ inhibiting MMP-9 gene expression and enzymatic activity occurred at transcriptional regulation. Mechanistically, activation of ERK and AKT is crucial for MMP-9 gene expression, and the addition of ANQ suppressed phosphorylation of ERK and AKT. The induction of the AP-1 and NF-κB pathway participated in MMP-9 gene expression. Suppression of ERK inhibited AP-1, whereas blocking AKT diminished NF-κB activity, and treatment with ANQ suppressed both AP-1 and NF-κB signaling. Moreover, ANQ suppressed EMT protein expression, and inhibited TPA-induced EMT through downregulating the ERK-AP-1 and AKT-NF-κB signaling cascades. Together, our data showed for the first time that ANQ inhibited breast cancer invasiveness by suppressing ERK-AP-1- and AKT-NF-κB-dependent MMP-9 and EMT expressions. |
| Databáze: | OpenAIRE |
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