Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c‐Myc axis in gastric cancer
Abstract Gastric cancer (GC) is one of the most familiar malignancy in the digestive system. Demethylzeylasteral (Dem), a natural functional monomer extracted from Tripterygium wilfordii Hook F, shows anti‐tumor effects in a variety of cancers, including GC, however, with the underlying mechanism po...
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.73 |
| _version_ | 1818589036687654912 |
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| author | Yongsen Li Yongyue Su Yuzu Zhao Xiaosong Hu Gaichao Zhao Jiang He Sicheng Wan Muhan Lü Hongjuan Cui |
| author_facet | Yongsen Li Yongyue Su Yuzu Zhao Xiaosong Hu Gaichao Zhao Jiang He Sicheng Wan Muhan Lü Hongjuan Cui |
| author_sort | Yongsen Li |
| collection | DOAJ |
| description | Abstract Gastric cancer (GC) is one of the most familiar malignancy in the digestive system. Demethylzeylasteral (Dem), a natural functional monomer extracted from Tripterygium wilfordii Hook F, shows anti‐tumor effects in a variety of cancers, including GC, however, with the underlying mechanism poorly understood. In our study, we show that Dem inhibits the proliferation, migration, and invasion of GC cells, which are mediated by down‐regulating c‐Myc protein levels. Mechanistically, Dem reduces the stability of c‐Myc by up‐regulating FBXW7, an E3 ubiquitin ligase. Moreover, in xenograft tumor model experiment, Dem also inhibits GC, which depends on suppressing c‐Myc expression. Finally, Dem enhances GC cell chemosensitivity to the combination treatment of 5‐Fluorouracil (5‐Fu) and doxorubicin (DOX) in vitro. Together, Dem exerts anti‐neoplastic activities through destabilizing and suppressing c‐Myc, establishing a theory foundation for using it in future treatment of GC. |
| first_indexed | 2024-12-16T09:34:16Z |
| format | Article |
| id | doaj.art-41feeb044e9d4c74bada690ec191b05c |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-12-16T09:34:16Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
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| series | MedComm |
| spelling | doaj.art-41feeb044e9d4c74bada690ec191b05c2022-12-21T22:36:26ZengWileyMedComm2688-26632021-09-012346748010.1002/mco2.73Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c‐Myc axis in gastric cancerYongsen Li0Yongyue Su1Yuzu Zhao2Xiaosong Hu3Gaichao Zhao4Jiang He5Sicheng Wan6Muhan Lü7Hongjuan Cui8State Key Laboratory of Silkworm Genome Biology College of Sericulture Textile and Biomass sciences Southwest University Chongqing ChinaDepartment of Orthopaedic 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army Kunming ChinaState Key Laboratory of Silkworm Genome Biology College of Sericulture Textile and Biomass sciences Southwest University Chongqing ChinaState Key Laboratory of Silkworm Genome Biology College of Sericulture Textile and Biomass sciences Southwest University Chongqing ChinaState Key Laboratory of Silkworm Genome Biology College of Sericulture Textile and Biomass sciences Southwest University Chongqing ChinaState Key Laboratory of Silkworm Genome Biology College of Sericulture Textile and Biomass sciences Southwest University Chongqing ChinaState Key Laboratory of Silkworm Genome Biology College of Sericulture Textile and Biomass sciences Southwest University Chongqing ChinaDepartment of Gastroenterology The Affiliated Hospital of Southwest Medical University Luzhou ChinaState Key Laboratory of Silkworm Genome Biology College of Sericulture Textile and Biomass sciences Southwest University Chongqing ChinaAbstract Gastric cancer (GC) is one of the most familiar malignancy in the digestive system. Demethylzeylasteral (Dem), a natural functional monomer extracted from Tripterygium wilfordii Hook F, shows anti‐tumor effects in a variety of cancers, including GC, however, with the underlying mechanism poorly understood. In our study, we show that Dem inhibits the proliferation, migration, and invasion of GC cells, which are mediated by down‐regulating c‐Myc protein levels. Mechanistically, Dem reduces the stability of c‐Myc by up‐regulating FBXW7, an E3 ubiquitin ligase. Moreover, in xenograft tumor model experiment, Dem also inhibits GC, which depends on suppressing c‐Myc expression. Finally, Dem enhances GC cell chemosensitivity to the combination treatment of 5‐Fluorouracil (5‐Fu) and doxorubicin (DOX) in vitro. Together, Dem exerts anti‐neoplastic activities through destabilizing and suppressing c‐Myc, establishing a theory foundation for using it in future treatment of GC.https://doi.org/10.1002/mco2.73chemosensitivityc‐MycdemethylzeylasteralFBXW7gastric cancer |
| spellingShingle | Yongsen Li Yongyue Su Yuzu Zhao Xiaosong Hu Gaichao Zhao Jiang He Sicheng Wan Muhan Lü Hongjuan Cui Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c‐Myc axis in gastric cancer MedComm chemosensitivity c‐Myc demethylzeylasteral FBXW7 gastric cancer |
| title | Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c‐Myc axis in gastric cancer |
| title_full | Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c‐Myc axis in gastric cancer |
| title_fullStr | Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c‐Myc axis in gastric cancer |
| title_full_unstemmed | Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c‐Myc axis in gastric cancer |
| title_short | Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c‐Myc axis in gastric cancer |
| title_sort | demethylzeylasteral inhibits proliferation migration and invasion through fbxw7 c myc axis in gastric cancer |
| topic | chemosensitivity c‐Myc demethylzeylasteral FBXW7 gastric cancer |
| url | https://doi.org/10.1002/mco2.73 |
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