Antcin‐H Isolated from Antrodia cinnamomea Inhibits Renal Cancer Cell Invasion Partly through Inactivation of FAK‐ERK‐C/EBP‐β/c‐Fos‐MMP‐7 Pathways

Antcin‐H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, Antrodia cinnamomea, in Taiwan. This study showed that antcin‐H inhibited the growth of human renal carcinoma 786‐0 cells; the IC 50 value (for 48 h) was 170 μ M. Besides, the migration and invasion of 786‐0 cells were suppressed by antcin‐H under noncytotoxic concentrations (<100 μ M); these events were accompanied by inhibition of FAK and Src kinase activities, decrease of paxillin phosphorylation, impairment of lamellipodium formation, and upregulation of TIMPs and downregulation of MMPs, especially MMP‐7 expression. Luciferase reporter assay showed that antcin‐H repressed the MMP‐7 promoter activity, in parallel to inhibiting c‐Fos/AP‐1 and C/EBP‐ β transactivation abilities. Moreover, antcin‐H suppressed the activity of ERK1/2 and decreased the binding ability of C/EBP‐ β and c‐Fos on the upstream/enhancer region of MMP‐7 promoter. Overall, this study demonstrated that the anti‐invasive effect of antcin‐H in human renal carcinoma 786‐0 cells might be at least in part by abrogating focal adhesion complex and lamellipodium formation through inhibiting the Src/FAK‐paxillin signaling pathways and decreasing MMP‐7 expression through suppressing the ERK1/2‐AP‐1/c‐Fos and C/EBP‐ β signaling axis. Our findings provide the evidence that antcin‐H may be an active component existing in A. cinnamomea with anticancer effect.