Cancer is a serious disease with a complex pathogenesis, which threats human life greatly. Angiogenesis is directly involved in invasion and metastasis of cancer. This study reveals the effect of fucodiphloroethol G isolated from Ecklonia cava, a marine brown alga on angiogenesis through inhibiting proteinase enzymes; AP-N, MMP-2, -9 and transcriptional factor; c-fos, together with underling molecular mechanisms. The results showed that fucodiphloroethol G inhibited the activity AP-N dose dependently. Moreover, expression of MMP-2, -9 was significantly inhibited at both protein and gene levels. The responsible transcriptional factor for the activation of AP-N and MMPs, c-fos protein was significantly inhibited by the treatment of fucodiphloroethol G. Furthermore, effects of fucodiphloroethol Con signaling pathways such as MAPK and Akt, related to activation of transcription of AP-N. MMPs and c-fos were observed. Fucodiphloroethol G showed a significant inhibition on molecules of MAPK pathway; MEK. ERK, and p38, and Akt, but not JNK. Collectively, these results demonstrate the potential anti-angiogenic effect of fucodiphloroethol G on VEGF induced ECV-304 and EA.hy926 through inhibition of AP-N, MMP-2, -9, c-fos via blocking of signal transduction of MAPK and Akt pathways. Therefore, fucodiphloroethol G could be used as a potential therapeutic target in the treatment of angiogenesis. (C) 2011 Elsevier Ltd. All rights reserved.