Ursolic Acid Alleviates Cancer Cachexia and Prevents Muscle Wasting via Activating SIRT1
Skeletal muscle wasting is the most remarkable phenotypic feature of cancer cachexia that increases the risk of morbidity and mortality. However, there are currently no effective drugs against cancer cachexia. Ursolic acid (UA) is a lipophilic pentacyclic triterpene that has been reported to allevia...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/8/2378 |
| _version_ | 1797605976299274240 |
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| author | Weili Tao Ze Ouyang Zhiqi Liao Lu Li Yujie Zhang Jiali Gao Li Ma Shiying Yu |
| author_facet | Weili Tao Ze Ouyang Zhiqi Liao Lu Li Yujie Zhang Jiali Gao Li Ma Shiying Yu |
| author_sort | Weili Tao |
| collection | DOAJ |
| description | Skeletal muscle wasting is the most remarkable phenotypic feature of cancer cachexia that increases the risk of morbidity and mortality. However, there are currently no effective drugs against cancer cachexia. Ursolic acid (UA) is a lipophilic pentacyclic triterpene that has been reported to alleviate muscle atrophy and reduce muscle decomposition in some disease models. This study aimed to explore the role and mechanisms of UA treatment in cancer cachexia. We found that UA attenuated Lewis lung carcinoma (LLC)-conditioned medium-induced C2C12 myotube atrophy and muscle wasting of LLC tumor-bearing mice. Moreover, UA dose-dependently activated SIRT1 and downregulated MuRF1 and Atrogin-1. Molecular docking results revealed a good binding effect on UA and SIRT1 protein. UA rescued vital features wasting without impacting tumor growth, suppressed the elevated spleen weight, and downregulated serum concentrations of inflammatory cytokines in vivo. The above phenomena can be attenuated by Ex-527, an inhibitor of SIRT1. Furthermore, UA remained protective against cancer cachexia in the advanced stage of tumor growth. The results revealed that UA exerts an anti-cachexia effect via activating SIRT1, thereby downregulating the phosphorylation levels of NF-κB and STAT3. UA might be a potential drug against cancer cachexia. |
| first_indexed | 2024-03-11T05:09:49Z |
| format | Article |
| id | doaj.art-25ec3b060195459bad18bf2de2cf319a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:09:49Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-25ec3b060195459bad18bf2de2cf319a2023-11-17T18:40:08ZengMDPI AGCancers2072-66942023-04-01158237810.3390/cancers15082378Ursolic Acid Alleviates Cancer Cachexia and Prevents Muscle Wasting via Activating SIRT1Weili Tao0Ze Ouyang1Zhiqi Liao2Lu Li3Yujie Zhang4Jiali Gao5Li Ma6Shiying Yu7Department of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, ChinaReproductive Medicine Center, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, ChinaDivision of Respiratory and Critical Care Medicine, Department of Internal Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, ChinaSkeletal muscle wasting is the most remarkable phenotypic feature of cancer cachexia that increases the risk of morbidity and mortality. However, there are currently no effective drugs against cancer cachexia. Ursolic acid (UA) is a lipophilic pentacyclic triterpene that has been reported to alleviate muscle atrophy and reduce muscle decomposition in some disease models. This study aimed to explore the role and mechanisms of UA treatment in cancer cachexia. We found that UA attenuated Lewis lung carcinoma (LLC)-conditioned medium-induced C2C12 myotube atrophy and muscle wasting of LLC tumor-bearing mice. Moreover, UA dose-dependently activated SIRT1 and downregulated MuRF1 and Atrogin-1. Molecular docking results revealed a good binding effect on UA and SIRT1 protein. UA rescued vital features wasting without impacting tumor growth, suppressed the elevated spleen weight, and downregulated serum concentrations of inflammatory cytokines in vivo. The above phenomena can be attenuated by Ex-527, an inhibitor of SIRT1. Furthermore, UA remained protective against cancer cachexia in the advanced stage of tumor growth. The results revealed that UA exerts an anti-cachexia effect via activating SIRT1, thereby downregulating the phosphorylation levels of NF-κB and STAT3. UA might be a potential drug against cancer cachexia.https://www.mdpi.com/2072-6694/15/8/2378ursolic acidcancer cachexiaskeletal muscleSIRT1Ex-527NF-κB |
| spellingShingle | Weili Tao Ze Ouyang Zhiqi Liao Lu Li Yujie Zhang Jiali Gao Li Ma Shiying Yu Ursolic Acid Alleviates Cancer Cachexia and Prevents Muscle Wasting via Activating SIRT1 Cancers ursolic acid cancer cachexia skeletal muscle SIRT1 Ex-527 NF-κB |
| title | Ursolic Acid Alleviates Cancer Cachexia and Prevents Muscle Wasting via Activating SIRT1 |
| title_full | Ursolic Acid Alleviates Cancer Cachexia and Prevents Muscle Wasting via Activating SIRT1 |
| title_fullStr | Ursolic Acid Alleviates Cancer Cachexia and Prevents Muscle Wasting via Activating SIRT1 |
| title_full_unstemmed | Ursolic Acid Alleviates Cancer Cachexia and Prevents Muscle Wasting via Activating SIRT1 |
| title_short | Ursolic Acid Alleviates Cancer Cachexia and Prevents Muscle Wasting via Activating SIRT1 |
| title_sort | ursolic acid alleviates cancer cachexia and prevents muscle wasting via activating sirt1 |
| topic | ursolic acid cancer cachexia skeletal muscle SIRT1 Ex-527 NF-κB |
| url | https://www.mdpi.com/2072-6694/15/8/2378 |
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