Lee Wai-Theng, Lee Tzong-Huei, Cheng Chia-Hsiung, Chen Ku-Chung, Chen Yen-Chou, Lin Cheng-Wei
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Institute of Fisheries Science, National Taiwan University, Taipei, Taiwan.
Food Chem Toxicol. 2015 Apr;78:33-41. doi: 10.1016/j.fct.2015.01.012. Epub 2015 Feb 2.
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.
antroquinonol（ANQ）是一种从樟芝菌丝体中分离出的泛醌衍生物。然而，ANQ对乳腺癌治疗的作用尚不清楚。我们发现，ANQ显著抑制乳腺癌MDA-MB-231细胞的迁移和侵袭，并抑制12-氧-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的MCF7细胞侵袭性。ANQ对MMP-9基因表达和酶活性的抑制作用发生在转录调控水平。机制上，ERK和AKT的激活对MMP-9基因表达至关重要，添加ANQ可抑制ERK和AKT的磷酸化。AP-1和NF-κB信号通路的激活参与了MMP-9基因表达。抑制ERK可抑制AP-1，而阻断AKT可降低NF-κB活性，ANQ处理可同时抑制AP-1和NF-κB信号。此外，ANQ抑制EMT蛋白表达，并通过下调ERK-AP-1和AKT-NF-κB信号级联反应抑制TPA诱导的EMT。总之，我们的数据首次表明，ANQ通过抑制ERK-AP-1和AKT-NF-κB依赖的MMP-9和EMT表达来抑制乳腺癌的侵袭性。
