Antcin-H Isolated from Antrodia cinnamomea Inhibits Renal Cancer Cell Invasion Partly through Inactivation of FAK-ERK-CEBP-βc-Fos-MMP-7 Pathways

الملخص EN

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 IC50 value (for 48 h) was 170 μM.

Besides, the migration and invasion of 786-0 cells were suppressed by antcin-H under noncytotoxic concentrations (<100 μM); 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.