Pentapeptide AYP from Isochrysis Zhanjiangensis Exhibits Antiangiogenic Activity in HT1080 Cells and HUVECs by Suppressing Migration and Invasion In Vitro

Microalgae are important biological sources of marine active peptides and renewable biological resources. Isochrysis zhanjiangensis has been widely used in biological ultrafiltration membranes and aquaculture. However, there are relatively few studies on its component structure and diverse activities. In this study, the mechanism of action of previously isolated pentapeptides (AYP, Ala-Tyr-Ala-Pro-Glu) on inflammation and tumor angiogenesis was evaluated. The results showed that AYP could effectively inhibit the invasion and migration of human umbilical vein endothelial cells (HUVECs) and HT1080 cells by downregulating the expression of MMP-2/-9, independent of cytotoxicity. Especially after 100 μM AYP treatment, the ability to inhibit migration was about 67.7% ± 1.9 for HT1080 cells and 63.6% ± 1.3 for HUVECs, respectively. In addition, the activity of iNOS and COX-2 was decreased by inhibiting the oversecretion of VEGF in HT1080 cells induced by CoCl2 and the activation of VEGFR-2 in HUVECs and by regulating PI3K/AKT and Ras/MAPK signaling pathways. It can prevent inflammation and block tumor angiogenesis. Therefore, AYP is expected to become a drug or functional food to prevent and treat tumor angiogenesis.