School of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.
Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Shenzhen 518108, China.
Mar Drugs. 2023 Feb 26;21(3):156. doi: 10.3390/md21030156.
Epi-aszonalenin A (EAA) is an alkaloid that is isolated and purified from the secondary metabolites of coral symbiotic fungi and has been shown to have good atherosclerotic intervention activity and anti-angiogenic activity in our previous studies. In the present study, antiangiogenic activity was used as a basis of an intensive study of its mechanism of action against tumor metastasis and invasion. Invasive metastatic pairs are a hallmark of malignancy, and the dissemination of tumor cells is the most dangerous process in the development of tumors. The results of cell wound healing and the Transwell chamber assay showed that EAA interfered well with PMA-induced migration and invasion of HT1080 cells. Western blot and the ELISA assay showed that EAA decreased MMPs and vascular endothelial growth factor (VEGF) activity and inhibited the expression of N-cadherin and hypoxia-inducible factor-1α (HIF-1α) by regulating the phosphorylation of downstream mitogen-activated protein kinase (MAPK), PI3K/AKT, and NF-κB pathways. Simultaneous molecular docking results revealed that the mimic coupling between the EAA and MMP-2/-9 molecules formed a stable interaction. The results of this study provide a research basis for the inhibition of tumor metastasis by EAA, and together with previous studies, confirm the potential pharmacology and drug potential for this class of compound for application in angiogenesis-related diseases and further improve the availability of coral symbiotic fungi.
表阿扎林 A（EAA）是一种生物碱，从珊瑚共生真菌的次级代谢产物中分离和纯化得到，在我们之前的研究中显示出良好的抗动脉粥样硬化干预活性和抗血管生成活性。在本研究中，抗血管生成活性被用作其针对肿瘤转移和侵袭作用机制的深入研究基础。侵袭性转移对是恶性肿瘤的标志，肿瘤细胞的扩散是肿瘤发展过程中最危险的过程。细胞划痕愈合和 Transwell 室分析的结果表明，EAA 很好地干扰了 PMA 诱导的 HT1080 细胞的迁移和侵袭。Western blot 和 ELISA 分析表明，EAA 通过调节下游丝裂原活化蛋白激酶（MAPK）、PI3K/AKT 和 NF-κB 通路的磷酸化，降低 MMPs 和血管内皮生长因子（VEGF）活性，抑制 N-钙黏蛋白和缺氧诱导因子-1α（HIF-1α）的表达。同时的分子对接结果表明，EAA 与 MMP-2/-9 分子的模拟偶联形成了稳定的相互作用。本研究结果为 EAA 抑制肿瘤转移提供了研究基础，与之前的研究一起，证实了该类化合物在血管生成相关疾病中的应用具有潜在的药理学和药物潜力，进一步提高了珊瑚共生真菌的可用性。
