Abstract
Although scientific evidences are lacking, Antrodia cinnamomea is widely prescribed in Taiwan as an adjuvant to cancer chemotherapy including hepatocellular carcinoma (HCC).We therefore hypothesize that ethanol extract of fruiting bodies of Antrodia cinnamomea (EEAC) is able to modulate migration and invasion to human HCC including HepG2 and Hep3B. Our results demonstrate that non-toxic EEAC exhibit an inhibitory effect on cell migration and invasion of HCC. Gelatin zymography assays confirmed that non-toxic EEAC repressed the activities of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-14. Western blotting data illustrated that non-toxic EEAC decreased the expression of MMP-2, MMP-9, and MMP-14; while the expression of the endogenous inhibitors of these proteins, i.e., tissue inhibitors of MMP (TIMP-1 and TIMP-2) increased. Additional, non-toxic EEAC inhibited the phosphorylation of ERK1/2, p38, and JNK1/2. Non-toxic EEAC inhibited the phosphorylation of FAK and Akt. Besides, treatment of zhankuic acid A, and cordycepin, active ingredients from EEAC decreased the expression of MMP-2, and MMP-9 through a MAPK, FAK and AKT signaling pathway. Our in vivo study, EEAC-treated animals demonstrate less tumor volume and immunohistochemical MMP-2, MMP-9 and MMP-14 expressions. Clinically, these results may propose further insight into the molecular mechanisms of EEAC as an adjuvant to human HCC cells.
Keywords: Antrodia cinnamomea; hepatocellular carcinoma; Metastasis; Invasion; Matrix metalloproteinase
