Targeting fucosyltransferase FUT8 as a prospective therapeutic approach for DLBCL
Abstract Diffuse large B-cell lymphoma (DLBCL) is characterized by its aggressive nature and resistance to standard chemotherapy, necessitating the development of new therapeutic approaches. The emergence of natural products and their derivatives has notably influenced cancer treatment, making morus...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Oncogenesis |
| Online Access: | https://doi.org/10.1038/s41389-025-00544-7 |
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| author | Hao Xu Qi Li Yuchen Zhang Chuan He Xinyun Zhang Zhiming Wang Meifang Zhao Yali Chai Wenzhuo Zhuang Bingzong Li |
| author_facet | Hao Xu Qi Li Yuchen Zhang Chuan He Xinyun Zhang Zhiming Wang Meifang Zhao Yali Chai Wenzhuo Zhuang Bingzong Li |
| author_sort | Hao Xu |
| collection | DOAJ |
| description | Abstract Diffuse large B-cell lymphoma (DLBCL) is characterized by its aggressive nature and resistance to standard chemotherapy, necessitating the development of new therapeutic approaches. The emergence of natural products and their derivatives has notably influenced cancer treatment, making morusinol, a medicine-derived monomer, a promising candidate. Here, we showed that morusinol exerted antitumor effects on DLBCL in vitro by inducing apoptosis and cell cycle arrest. Impressively, morusinol treatment exhibited potent tumor growth inhibition in vivo, proving both well-tolerated and safe in mouse models. Moreover, our investigation identified FUT8, a fucosyltransferase, as a potential target for morusinol. FUT8’s role as an oncogene in DLBCL and its correlation with poor survival further underscored its significance. Furthermore, our screening efforts involving clinical and preclinical drugs unveiled a compelling synergistic effect between chidamide and morusinol. Additionally, morusinol’s ability to hinder M2-like polarization of tumor-associated macrophages suggested its potential in immune response modulation within DLBCL. Collectively, morusinol showcased substantial promise as an anti-tumor agent for potential clinical application in DLBCL management, potentially augmenting established therapeutic strategies. Moreover, our findings offered promising prospects for natural products to effectively leverage its therapeutic advantages. Working model: The role of Morusinol in treating DLBCL. |
| format | Article |
| id | doaj-art-09c1955fba4042bfb3b8559ffa1ce958 |
| institution | Kabale University |
| issn | 2157-9024 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Oncogenesis |
| spelling | doaj-art-09c1955fba4042bfb3b8559ffa1ce9582025-02-02T12:43:10ZengNature Publishing GroupOncogenesis2157-90242025-01-0114111010.1038/s41389-025-00544-7Targeting fucosyltransferase FUT8 as a prospective therapeutic approach for DLBCLHao Xu0Qi Li1Yuchen Zhang2Chuan He3Xinyun Zhang4Zhiming Wang5Meifang Zhao6Yali Chai7Wenzhuo Zhuang8Bingzong Li9Department of Hematology, The Second Affiliated Hospital of Soochow UniversityDepartment of Hematology, The Second Affiliated Hospital of Soochow UniversityDepartment of Hematology, The Second Affiliated Hospital of Soochow UniversityDepartment of Hematology, The Second Affiliated Hospital of Soochow UniversityDepartment of Hematology, The Second Affiliated Hospital of Soochow UniversityDepartment of Cell Biology, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow UniversityDepartment of Hematology, The Second Affiliated Hospital of Soochow UniversityDepartment of Cell Biology, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow UniversityDepartment of Cell Biology, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow UniversityDepartment of Hematology, The Second Affiliated Hospital of Soochow UniversityAbstract Diffuse large B-cell lymphoma (DLBCL) is characterized by its aggressive nature and resistance to standard chemotherapy, necessitating the development of new therapeutic approaches. The emergence of natural products and their derivatives has notably influenced cancer treatment, making morusinol, a medicine-derived monomer, a promising candidate. Here, we showed that morusinol exerted antitumor effects on DLBCL in vitro by inducing apoptosis and cell cycle arrest. Impressively, morusinol treatment exhibited potent tumor growth inhibition in vivo, proving both well-tolerated and safe in mouse models. Moreover, our investigation identified FUT8, a fucosyltransferase, as a potential target for morusinol. FUT8’s role as an oncogene in DLBCL and its correlation with poor survival further underscored its significance. Furthermore, our screening efforts involving clinical and preclinical drugs unveiled a compelling synergistic effect between chidamide and morusinol. Additionally, morusinol’s ability to hinder M2-like polarization of tumor-associated macrophages suggested its potential in immune response modulation within DLBCL. Collectively, morusinol showcased substantial promise as an anti-tumor agent for potential clinical application in DLBCL management, potentially augmenting established therapeutic strategies. Moreover, our findings offered promising prospects for natural products to effectively leverage its therapeutic advantages. Working model: The role of Morusinol in treating DLBCL.https://doi.org/10.1038/s41389-025-00544-7 |
| spellingShingle | Hao Xu Qi Li Yuchen Zhang Chuan He Xinyun Zhang Zhiming Wang Meifang Zhao Yali Chai Wenzhuo Zhuang Bingzong Li Targeting fucosyltransferase FUT8 as a prospective therapeutic approach for DLBCL Oncogenesis |
| title | Targeting fucosyltransferase FUT8 as a prospective therapeutic approach for DLBCL |
| title_full | Targeting fucosyltransferase FUT8 as a prospective therapeutic approach for DLBCL |
| title_fullStr | Targeting fucosyltransferase FUT8 as a prospective therapeutic approach for DLBCL |
| title_full_unstemmed | Targeting fucosyltransferase FUT8 as a prospective therapeutic approach for DLBCL |
| title_short | Targeting fucosyltransferase FUT8 as a prospective therapeutic approach for DLBCL |
| title_sort | targeting fucosyltransferase fut8 as a prospective therapeutic approach for dlbcl |
| url | https://doi.org/10.1038/s41389-025-00544-7 |
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