The Antitumor Activity of Antrodia camphorata in Melanoma Cells: Modulation of Wnt//beta-Catenin Signaling Pathways

摘要

Antrodia camphorata (AC) is well known in Taiwan as a traditional Chinese medicine. The aim of this study was to investigate whether a fermented culture broth of AC could inhibit melanoma proliferation and progression via suppression of the Wnt/beta-catenin signaling pathway. In this study, we observed that AC treatment resulted in decreased cell viability and disturbed Wnt/beta-catenin cascade in B16F10 and/or B16F1 melanoma cells. This result was accompanied by a decrease in the expression of Wnt/beta-catenin transcriptional targets, including c-Myc and survivin. Furthermore, treatment of melanoma cells with AC resulted in a significant increase in apoptosis, which was associated with DNA fragmentation, cytochrome c release, caspase-9 and -3 activation, PARP degradation, Bcl-2/Bax dysregulation, and p53 expression. We also observed that AC caused d phase arrest mediated by a downregulation of cyclin Dl and CDK4 and increased p21 and p27 expression. In addition, we demonstrated that non- and subcytotoxic concentrations of AC markedly inhibited migration and invasion of highly metastatic B16F10 cells. The antimetastatic effect of AC was further confirmed by reductions in the levels of MMP-2, MMP-9, and VEGF expression. These results suggest that Antrodia camphorata may exert antitumor activity by downregulating the Wnt/beta-catenin pathways.