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Food Chem Toxicol. 2015 Apr;78:33-41. doi: 10.1016/j.fct.2015.01.012. Epub 2015 Feb 2.

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.

Author information

1
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
2
Institute of Fisheries Science, National Taiwan University, Taipei, Taiwan.
3
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
4
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
5
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: cwlin@tmu.edu.tw.

Abstract

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.

KEYWORDS:

Antroquinonol; EMT; Invasion; MMP-9; TPA

PMID:
25656647
DOI:
10.1016/j.fct.2015.01.012
[Indexed for MEDLINE]

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