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

Wai-Theng Lee; Tzong-Huei Lee; Chia-Hsiung Cheng; Ku-Chung Chen; Yen-Chou Chen; Cheng-Wei Lin

doi:10.1016/j.fct.2015.01.012

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

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

Authors

Wai-Theng Lee¹, Tzong-Huei Lee², Chia-Hsiung Cheng³, Ku-Chung Chen³, Yen-Chou Chen⁴, Cheng-Wei Lin⁵

Affiliations

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.

PMID: 25656647
DOI: 10.1016/j.fct.2015.01.012

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antrodia / chemistry
Breast Neoplasms / metabolism
Breast Neoplasms / pathology*
Cell Line, Tumor / drug effects
Cell Movement / drug effects*
Cell Survival / drug effects
Down-Regulation
Epithelial-Mesenchymal Transition / drug effects*
Humans
MCF-7 Cells / drug effects
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism*
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / genetics
Mitogen-Activated Protein Kinase 3 / metabolism*
NF-kappa B / antagonists & inhibitors
NF-kappa B / genetics
NF-kappa B / metabolism
Phosphorylation
Signal Transduction
Tetradecanoylphorbol Acetate / toxicity
Transcription Factor AP-1 / antagonists & inhibitors
Transcription Factor AP-1 / genetics
Transcription Factor AP-1 / metabolism*
Ubiquinone / analogs & derivatives*
Ubiquinone / pharmacology

Substances

NF-kappa B
Transcription Factor AP-1
Ubiquinone
antroquinonol
Mitogen-Activated Protein Kinase 3
MMP9 protein, human
Matrix Metalloproteinase 9
Tetradecanoylphorbol Acetate