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Laurencia undulata, as one of the most biologically active species in the genus Laurencia, is an edible folk herb red algae. Among them, d-isofloridoside (DIF, 940.68 Da) is isolated from Laurencia undulata, which has antioxidant and matrix metalloproteinases (MMP) inhibitory activities. However, its mechanism of action on tumor angiogenesis has not yet been reported. In this study, we have studied the mechanism of DIF on tumor metastasis and angiogenesis in HT1080 cell and human vascular endothelial cell (HUVEC). The results show that DIF can reduce the activity of MMP-2/9, and can inhibit the expression of hypoxia-inducible factor-1α (HIF-1α) by regulating the downstream PI3K/AKT and mitogen-activated protein kinases (MAPK) pathways, thereby down-regulating the production of vascular endothelial growth factor (VEGF) in CoCl2-induced HT1080 cell. In addition, DIF can inhibit the activation of VEGF receptor (VEGFR-2), regulate downstream PI3K/AKT, MAPK, nuclear factor-kappa B (NF-κB) signal pathways, activate apoptosis, and thus down-regulate the production of platelet-derived growth factor (PDGF) in VEGF-induced HUVEC. In conclusion, our research shows that DIF has the potential to develop into a tumor-preventing functional food and tumor angiogenesis inhibitor, and it can provide theoretical guidance for the high-value comprehensive utilization of edible red algae Laurencia undulata.

Microalgae are important biological sources of marine active peptides and renewable biological resources. Isochrysis zhanjiangensishas 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 CoCl2and 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.