Flavonoids from medicinal plants possess pharmacological effects for preventing tumor progression by inhibiting tumor-cell proliferation, neoplastic angiogenesis, and tumor invasion. We reported that a citrus polymethoxyflavonoid, nobiletin (5,6,7,8,3’,4’-hexamethoxy flavone) (Fig.1), exhibits antitumor-invasive and antitumorigenic actions in vivo and in vitro. In addition, water extract of Grifola frondosa (Maitake mushroom) has been reported to possess antitumor effects by enhancing the immune system. However, the anti-angiogenic actions of nobiletin and Maitake mushroom extract remain unclear. In the present study, we examined whether nobiletin and an ethanol extract of the Maitake mushroom (Maitake extract), which is termed Gripin® (Fig. 2), influenced the proliferation of human melanoma Mewo cells and the tube formation of human microvascular endothelial cells (HMVEC).