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. (April 2015)

• Record Type: Journal Article
• Authors: Lee, Wai-Theng; Lee, Tzong-Huei; Cheng, Chia-Hsiung; Chen, Ku-Chung; Chen, Yen-Chou; Lin, Cheng-Wei
• Is Part Of: Food and chemical toxicology. Volume 78(2015)
• Page Start: 33
• Page End: 41
• Publication Date: 2015-04
• Subjects: Antroquinonol -- EMT -- Invasion -- MMP-9 -- TPA; ANQ antroquinonol -- AP-1 activator protein-1 -- EMT epithelial-to mesenchymal transition -- ERK extracellular-regulated protein kinase -- JNK c-Jun N-terminal kinase -- MAPK mitogen-activated protein kinase -- MMP matrix metalloproteinase -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide -- NF-κB nuclear factor-kappa B -- TPA 12-O-tetradecanoylphorbol-13-acetate -- PI3K phosphoinositide 3-kinase; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2015.01.012
• Languages: English
• ISSNs: 0278-6915

Abstract

Highlights: Antroquinonol (ANQ) effectively inhibits breast cancer migration and invasion. ANQ suppression of tumor invasiveness through inhibiting MMP-9 gene transcription. ANQ downregulates ERK/AP-1- and AKT/NF-κB-dependent MMP-9 signaling pathway. ANQ suppresses the epithelial-mesenchymal transition in breast cancer cells. 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.