Ethanol Extracts of Fruiting Bodies of Antrodia cinnamomea Suppress CL1-5 Human Lung Adenocarcinoma Cells Migration by Inhibiting Matrix Metalloproteinase-29 through ERK, JNK, p38, and PI3KAkt Signaling Pathways

الملخص EN

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.