Ethanol extracts of fruiting bodies of Antrodia cinnamomea exhibit anti-migration action in human adenocarcinoma CL1-0 cells through the MAPK and PI3K/AKT signaling pathways

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 CL1-0 cells in the absence of cytotoxicity. The results of a gelatin zymography assay showed that A. cinnamomea suppressed the activity 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. Two major compounds from EEAC codycepin and zhankuic acid A alone and together inhibited MMP-9 and MMP-2 expressions. Further investigation revealed that A. cinnamomea suppressed the phosphorylation of p38, and JNK1/2. A. cinnamomea also suppressed the expressions of PI3K and phosphorylation of AKT. This is the first report confirming the anti-migration activity of this potentially beneficial mushroom against human lung adenocarcinoma CL1-0.