Premium
Ethanol extracts of fruiting bodies of Antrodia cinnamomea suppresses CL1‐5 human lung adenocarcinoma cells migration by inhibiting matrix metalloproteinase‐2/9 through ERK, JNK, p38 and PI3K/Akt signaling pathways
Author(s) -
Chen Ying-Yi,
Wu Chieh-Hsi,
Sheu Ming-Jyh
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1037.1
Subject(s) - p38 mitogen activated protein kinases , matrix metalloproteinase , mapk/erk pathway , protein kinase b , chemistry , pi3k/akt/mtor pathway , phosphorylation , western blot , matrix metalloproteinase inhibitor , kinase , biochemistry , signal transduction , gene
Cancer metastasis is a primary cause of cancer death. Antrodia cinnamomea (A. cinnamomea), a medicinal mushroom in Taiwan, has been shown antioxidant and anticancer activities. In this study, we first observed that ethanol extract of fruiting bodies of A. cinnamomea (EEAC) exerted a concentration‐dependent inhibitory effect on migration and motility of the highly metastatic CL1‐5 cells in the absence of cytotoxicity. The results of a gelatin zymography assay showed that A. cinnamomea suppressed the activities of matrix metalloproteinase (MMP)‐2 and MMP‐9 in a concentration‐dependent manner. Western blot results demonstrated that treatment with A. cinnamomea decreased the expression of MMP‐9 and MMP‐2; while the expression of the endogenous inhibitors of these proteins, i.e., tissue inhibitors of MMP (TIMP‐1 and TIMP‐2) increased. Further investigation revealed that A. cinnamomea suppressed the phosphorylation of ERK1/2, p38, and JNK1/2. A. cinnamomea also suppressed the expressions of PI3K and phosphorylation of Akt. Furthermore, treatment of CL 1–5 cells with inhibitors specific for PI3K (LY 294002), ERK1/2 (PD98059), JNK (SP600125) and p38 MAPK (SB203580) decreased the expression of MMP‐2, and MMP‐9. This is the first report confirming the anti‐migration activity of this potentially beneficial mushroom against human lung adenocarcinoma CL1‐5 cancer cells.