Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration
Metastasis is the leading cause of cancer-related death and a critical challenge in improving cancer treatment today. Circulating tumor cells (CTCs) adhesion to and across the vascular endothelium are critical steps in the establishment of micrometastatic foci away from the primary tumor. Therefore,...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.960375/full |
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| author | Weiyu Wang Weiyu Wang Weiyu Wang Chengbin Fu Chengbin Fu Mengting Lin Mengting Lin Mengting Lin Yusheng Lu Yusheng Lu Shu Lian Shu Lian Xiaodong Xie Xiaodong Xie Guiyu Zhou Guiyu Zhou Wulin Li Wulin Li Wulin Li Yiping Zhang Lee Jia Lee Jia Chunlian Zhong Chunlian Zhong Mingqing Huang |
| author_facet | Weiyu Wang Weiyu Wang Weiyu Wang Chengbin Fu Chengbin Fu Mengting Lin Mengting Lin Mengting Lin Yusheng Lu Yusheng Lu Shu Lian Shu Lian Xiaodong Xie Xiaodong Xie Guiyu Zhou Guiyu Zhou Wulin Li Wulin Li Wulin Li Yiping Zhang Lee Jia Lee Jia Chunlian Zhong Chunlian Zhong Mingqing Huang |
| author_sort | Weiyu Wang |
| collection | DOAJ |
| description | Metastasis is the leading cause of cancer-related death and a critical challenge in improving cancer treatment today. Circulating tumor cells (CTCs) adhesion to and across the vascular endothelium are critical steps in the establishment of micrometastatic foci away from the primary tumor. Therefore, we believe that interrupting CTCs adhesion to endothelium and transendothelial migration may efficiently prevent cancer metastasis. Fucoxanthin (Fx) is an algal carotenoid widely distributed in brown algae, macroalgae, and diatoms. Previous studies have found that Fx has various pharmacological activities, including antidiabetic, antioxidant, anti-inflammatory, anti-obesity, antimalarial, anticancer, and so on. However, it remains unclear whether Fx has a preventive effect on cancer metastasis. Here, we found that Fx interrupts breast cancer cells MCF-7 adhesion to endothelium and transendothelial migration, thus inhibiting CTCs-based pulmonary metastasis in vivo. The hetero-adhesion assay showed that Fx significantly inhibited the expression of inflammatory factor-induced cell adhesion molecules (CAMs) and the resulting adhesion between MCF-7 cells and endothelial cells. The wound-healing and transwell assays showed that Fx significantly inhibited the motility, invasion, and transendothelial migration abilities of MCF-7 cells. However, the same concentration of Fx did not significantly alter the cell viability, cell cycle, apoptosis, and ROS of breast cancer cells, thus excluding the possibility that Fx inhibits MCF-7 cell adhesion and transendothelial migration through cytotoxicity. Mechanistically, Fx inhibits the expression of CAMs on endothelial cells by inhibiting the NF-кB signaling pathway by down-regulating the phosphorylation level of IKK-α/β, IкB-α, and NF-кB p65. Fx inhibits transendothelial migration of MCF-7 cells by inhibiting Epithelial-to-mesenchymal transition (EMT), PI3K/AKT, and FAK/Paxillin signaling pathways. Moreover, we demonstrated that Fx significantly inhibits the formation of lung micrometastatic foci in immunocompetent syngeneic mouse breast cancer metastasis models. We also showed that Fx enhances antitumor immune responses by substantially increasing the subsets of cytotoxic T lymphocytes in the peripheral immune system. This new finding provides a basis for the application of Fx in cancer metastatic chemoprevention and suggests that interruption of the CTCs adhesion to endothelium and transendothelial migration may serve as a new avenue for cancer metastatic chemoprevention. |
| first_indexed | 2024-04-12T23:10:27Z |
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| language | English |
| last_indexed | 2024-04-12T23:10:27Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-5458f2981995463c94de766883ff150b2022-12-22T03:12:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.960375960375Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migrationWeiyu Wang0Weiyu Wang1Weiyu Wang2Chengbin Fu3Chengbin Fu4Mengting Lin5Mengting Lin6Mengting Lin7Yusheng Lu8Yusheng Lu9Shu Lian10Shu Lian11Xiaodong Xie12Xiaodong Xie13Guiyu Zhou14Guiyu Zhou15Wulin Li16Wulin Li17Wulin Li18Yiping Zhang19Lee Jia20Lee Jia21Chunlian Zhong22Chunlian Zhong23Mingqing Huang24Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, ChinaDepartment of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, ChinaBreast Surgery Institute, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, ChinaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, ChinaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, ChinaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, ChinaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, ChinaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, ChinaCollege of Chemistry, Fuzhou University, Fuzhou, ChinaTechnical Innovation Center for Utilization of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, ChinaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, ChinaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory on Conservation and Sustainable Utilization of Marine Biodiversity, Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, ChinaFujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaMetastasis is the leading cause of cancer-related death and a critical challenge in improving cancer treatment today. Circulating tumor cells (CTCs) adhesion to and across the vascular endothelium are critical steps in the establishment of micrometastatic foci away from the primary tumor. Therefore, we believe that interrupting CTCs adhesion to endothelium and transendothelial migration may efficiently prevent cancer metastasis. Fucoxanthin (Fx) is an algal carotenoid widely distributed in brown algae, macroalgae, and diatoms. Previous studies have found that Fx has various pharmacological activities, including antidiabetic, antioxidant, anti-inflammatory, anti-obesity, antimalarial, anticancer, and so on. However, it remains unclear whether Fx has a preventive effect on cancer metastasis. Here, we found that Fx interrupts breast cancer cells MCF-7 adhesion to endothelium and transendothelial migration, thus inhibiting CTCs-based pulmonary metastasis in vivo. The hetero-adhesion assay showed that Fx significantly inhibited the expression of inflammatory factor-induced cell adhesion molecules (CAMs) and the resulting adhesion between MCF-7 cells and endothelial cells. The wound-healing and transwell assays showed that Fx significantly inhibited the motility, invasion, and transendothelial migration abilities of MCF-7 cells. However, the same concentration of Fx did not significantly alter the cell viability, cell cycle, apoptosis, and ROS of breast cancer cells, thus excluding the possibility that Fx inhibits MCF-7 cell adhesion and transendothelial migration through cytotoxicity. Mechanistically, Fx inhibits the expression of CAMs on endothelial cells by inhibiting the NF-кB signaling pathway by down-regulating the phosphorylation level of IKK-α/β, IкB-α, and NF-кB p65. Fx inhibits transendothelial migration of MCF-7 cells by inhibiting Epithelial-to-mesenchymal transition (EMT), PI3K/AKT, and FAK/Paxillin signaling pathways. Moreover, we demonstrated that Fx significantly inhibits the formation of lung micrometastatic foci in immunocompetent syngeneic mouse breast cancer metastasis models. We also showed that Fx enhances antitumor immune responses by substantially increasing the subsets of cytotoxic T lymphocytes in the peripheral immune system. This new finding provides a basis for the application of Fx in cancer metastatic chemoprevention and suggests that interruption of the CTCs adhesion to endothelium and transendothelial migration may serve as a new avenue for cancer metastatic chemoprevention.https://www.frontiersin.org/articles/10.3389/fphar.2022.960375/fullfucoxanthin (CID: 5281239)cancer metastasis chemopreventiontransendothelial migrationcell adhesionepithelial-to-mesenchymal transition (EMT)NF-κB signaling pathway |
| spellingShingle | Weiyu Wang Weiyu Wang Weiyu Wang Chengbin Fu Chengbin Fu Mengting Lin Mengting Lin Mengting Lin Yusheng Lu Yusheng Lu Shu Lian Shu Lian Xiaodong Xie Xiaodong Xie Guiyu Zhou Guiyu Zhou Wulin Li Wulin Li Wulin Li Yiping Zhang Lee Jia Lee Jia Chunlian Zhong Chunlian Zhong Mingqing Huang Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration Frontiers in Pharmacology fucoxanthin (CID: 5281239) cancer metastasis chemoprevention transendothelial migration cell adhesion epithelial-to-mesenchymal transition (EMT) NF-κB signaling pathway |
| title | Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration |
| title_full | Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration |
| title_fullStr | Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration |
| title_full_unstemmed | Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration |
| title_short | Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration |
| title_sort | fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration |
| topic | fucoxanthin (CID: 5281239) cancer metastasis chemoprevention transendothelial migration cell adhesion epithelial-to-mesenchymal transition (EMT) NF-κB signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.960375/full |
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