College of Food Science and Technology, School of Chemistry and Environment, Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Zhanjiang, Guangdong 524088, China.
Key Laboratory of Tropical Crop Products Processing of Ministry of Agriculture and Rural Affairs, Agricultural Products Processing Research Institute, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524001, China.
J Agric Food Chem. 2021 Nov 24;69(46):13787-13795. doi: 10.1021/acs.jafc.1c05007. Epub 2021 Nov 12.
, as one of the most biologically active species in the genus , is an edible folk herb red algae. Among them, d-isofloridoside (DIF, 940.68 Da) is isolated from , 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 CoCl-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 .
作为该属中生物活性最强的物种之一，是一种可食用的民间草药红藻。其中，D-异佛尔酮糖苷（DIF，940.68 Da）是从 中分离出来的，具有抗氧化和基质金属蛋白酶（MMP）抑制活性。然而，其对肿瘤血管生成的作用机制尚未报道。在本研究中，我们研究了 DIF 对 HT1080 细胞和人血管内皮细胞（HUVEC）肿瘤转移和血管生成的作用机制。结果表明，DIF 可以降低 MMP-2/9 的活性，并通过调节下游的 PI3K/AKT 和丝裂原活化蛋白激酶（MAPK）途径抑制缺氧诱导因子-1α（HIF-1α）的表达，从而下调 CoCl 诱导的 HT1080 细胞中血管内皮生长因子（VEGF）的产生。此外，DIF 可以抑制血管内皮生长因子受体（VEGFR-2）的激活，调节下游的 PI3K/AKT、MAPK、核因子-κB（NF-κB）信号通路，激活细胞凋亡，从而下调 VEGF 诱导的 HUVEC 中血小板衍生生长因子（PDGF）的产生。综上所述，我们的研究表明，DIF 具有开发成预防肿瘤的功能性食品和肿瘤血管生成抑制剂的潜力，可为可食用红藻的高值综合利用提供理论指导。
