Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 Cells
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 u...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/21/3/156 |
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| author | Yi Liu Liyuan Lin Haiyan Zheng Yuan-Lin He Yanmei Li Chunxia Zhou Pengzhi Hong Shengli Sun Yi Zhang Zhong-Ji Qian |
| author_facet | Yi Liu Liyuan Lin Haiyan Zheng Yuan-Lin He Yanmei Li Chunxia Zhou Pengzhi Hong Shengli Sun Yi Zhang Zhong-Ji Qian |
| author_sort | Yi Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:16:28Z |
| format | Article |
| id | doaj.art-9a8a4bf7db224ede8521a45260454f51 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-11T06:16:28Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-9a8a4bf7db224ede8521a45260454f512023-11-17T12:17:19ZengMDPI AGMarine Drugs1660-33972023-02-0121315610.3390/md21030156Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 CellsYi Liu0Liyuan Lin1Haiyan Zheng2Yuan-Lin He3Yanmei Li4Chunxia Zhou5Pengzhi Hong6Shengli Sun7Yi Zhang8Zhong-Ji Qian9School of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaSchool of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaSchool of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaSchool of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaSchool of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaSchool of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaSchool of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaSchool of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaSchool of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaSchool of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, ChinaEpi-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.https://www.mdpi.com/1660-3397/21/3/156alkaloidsneoplasm metastasismatrix metalloproteinasescell signaling |
| spellingShingle | Yi Liu Liyuan Lin Haiyan Zheng Yuan-Lin He Yanmei Li Chunxia Zhou Pengzhi Hong Shengli Sun Yi Zhang Zhong-Ji Qian Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 Cells Marine Drugs alkaloids neoplasm metastasis matrix metalloproteinases cell signaling |
| title | Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 Cells |
| title_full | Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 Cells |
| title_fullStr | Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 Cells |
| title_full_unstemmed | Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 Cells |
| title_short | Mechanisms of Antitumor Invasion and Metastasis of the Marine Fungal Derivative Epi-Aszonalenin A in HT1080 Cells |
| title_sort | mechanisms of antitumor invasion and metastasis of the marine fungal derivative epi aszonalenin a in ht1080 cells |
| topic | alkaloids neoplasm metastasis matrix metalloproteinases cell signaling |
| url | https://www.mdpi.com/1660-3397/21/3/156 |
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