Ethanol Extracts of Fruiting Bodies of Antrodia cinnamomea Suppress CL1-5 Human Lung Adenocarcinoma Cells Migration by Inhibiting Matrix Metalloproteinase-2/9 through ERK, JNK, p38, and PI3K/Akt Signaling Pathways

• Published in: Evidence-based complementary and alternative medicine 2012-01, Vol.2012 (2012), p.1-11
• Main Authors: Sheu, Ming-Jyh, Huang, Guan-Jhong, Chang, Wun-Shaing Wayne, Chien, Yi-Chung, Chou, Pei-Yu, Liu, Fon-Chang, Chen, Ying-Yi, Wu, Chieh-Hsi
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Adenocarcinoma; AKT protein; Antioxidants; Antrodia cinnamomea; Cell adhesion & migration; Cell culture; Cell migration; Chemistry; Cytotoxicity; Ethanol; Extracellular signal-regulated kinase; Fruit bodies; Gelatin; Gelatinase A; Gelatinase B; Inhibitors; Kinases; Lung cancer; MAP kinase; Matrix metalloproteinase; Medical research; Metalloproteinase; Metastases; Metastasis; Motility; Phosphorylation; Prostate cancer; Proteins; Signal transduction; Tissue inhibitor of metalloproteinase 1; Tissue inhibitor of metalloproteinase 2; Tumors; Vacuum distillation
• ISSN: 1741-427X; 1741-4288; 1741-4288
• DOI: 10.1155/2012/378415

Cancer metastasis is a primary cause of cancer death. Antrodia cinnamomea (A. cinnamomea), a medicinal mushroom in Taiwan, has 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, that is, 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 CL1-5 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 paper confirming the antimigration activity of this potentially beneficial mushroom against human lung adenocarcinoma CL1-5 cancer cells.