Anti-metastatic activities of Antrodia camphorata against human breast cancer cells mediated through suppression of the MAPK signaling pathway

作者:Yang Hsin Ling; Kuo Yueh Hsiung; Tsai Ching Tsan; Huang Yi Ting; Chen Ssu Ching; Chang Hsueh Wei; Lin Elong; Lin Wen Hsin; Hseu You Cheng*
来源:Food and Chemical Toxicology, 2011, 49(1): 290-298.
DOI:10.1016/j.fct.2010.10.031

摘要

The fermented culture broth of Antrodia camphorata (A. camphorata) has been shown to promote cell cycle arrest and apoptosis of human estrogen-nonresponsive MDA-MB-231 cells. Herein, we demonstrate that non-cytotoxic concentrations (20-80 mu g/mL) of A. camphorata markedly inhibited the invasion/migration of highly metastatic MDA-MB-231 cells as shown by an in vitro transwell and a wound-healing repair assay. The results of a gelatin zymography assay showed that A. camphorata suppressed the activity of matrix metalloproteinase (MMP)-9 and urokinase plasminogen activator (uPA). Western blot results demonstrated that treatment with A. camphorata decreased the expression of MMP-9, MMP-2, uPA, uPA receptor (uPAR) and vascular endothelial growth factor (VEGF); while the expression of the endogenous inhibitors of these proteins, i.e., tissue inhibitors of MMP (TIMP-1 and TIMP-2), and plasminogen activator inhibitor (PAI)-1, increased. Further investigation revealed that A. camphorata suppressed the phosphorylation of ERK1/2, p38, and JNK1/2. A. camphorata treatment also led to a dose-dependent inhibition on NF-kappa B binding and activation. This is the first report confirming the anti-metastatic activity of this potentially beneficial mushroom against human breast cancer.