Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling
Ophiobolin O is a member of ophiobolin family, which has been proved to be a potent anti-tumor drug candidate for human breast cancer. However, the anti-tumor effect and the mechanism of ophiobolin O remain unclear. In this study, we further verified ophiobolin O-induced G1 phase arrest in human bre...
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MDPI AG
2015-01-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/13/1/431 |
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| author | Cuiting Lv Wenxing Qin Tonghan Zhu Shanjian Wei Kui Hong Weiming Zhu Ruohua Chen Caiguo Huang |
| author_facet | Cuiting Lv Wenxing Qin Tonghan Zhu Shanjian Wei Kui Hong Weiming Zhu Ruohua Chen Caiguo Huang |
| author_sort | Cuiting Lv |
| collection | DOAJ |
| description | Ophiobolin O is a member of ophiobolin family, which has been proved to be a potent anti-tumor drug candidate for human breast cancer. However, the anti-tumor effect and the mechanism of ophiobolin O remain unclear. In this study, we further verified ophiobolin O-induced G1 phase arrest in human breast cancer MCF-7 cells, and found that ophiobolin O reduced the phosphorylation level of AKT and GSK3β, and induced down-regulation of cyclin D1. The inverse docking (INVDOCK) analysis indicated that ophiobolin O could bind to GSK3β, and GSK3β knockdown abolished cyclin D1 degradation and G1 phase arrest. Pre-treatment with phosphatase inhibitor sodium or thovanadate halted dephosphorylation of AKT and GSK3β, and blocked ophiobolin O-induced G1 phase arrest. These data suggest that ophiobolin O may induce G1 arrest in MCF-7 cells through interaction with AKT/GSK3β/cyclin D1 signaling. In vivo, ophiobolin O suppressed tumor growth and showed little toxicity in mouse xenograft models. Overall, these findings provide theoretical basis for the therapeutic use of ophiobolin O. |
| first_indexed | 2024-04-11T13:18:59Z |
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| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T13:18:59Z |
| publishDate | 2015-01-01 |
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| series | Marine Drugs |
| spelling | doaj.art-3d7a5d5c265143bfa41641bdff27632c2022-12-22T04:22:18ZengMDPI AGMarine Drugs1660-33972015-01-0113143144310.3390/md13010431md13010431Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 SignalingCuiting Lv0Wenxing Qin1Tonghan Zhu2Shanjian Wei3Kui Hong4Weiming Zhu5Ruohua Chen6Caiguo Huang7Department of Biochemistry and Molecular Biology, College of Basic Medical Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, ChinaTeaching Management Department, Yangpu Hospital, Tongji University School of Medicine, 450 Tengyue Road, Shanghai 200090, ChinaKey Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, ChinaVIP Medicine Department, Changhai Hospital, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, ChinaOphiobolin O is a member of ophiobolin family, which has been proved to be a potent anti-tumor drug candidate for human breast cancer. However, the anti-tumor effect and the mechanism of ophiobolin O remain unclear. In this study, we further verified ophiobolin O-induced G1 phase arrest in human breast cancer MCF-7 cells, and found that ophiobolin O reduced the phosphorylation level of AKT and GSK3β, and induced down-regulation of cyclin D1. The inverse docking (INVDOCK) analysis indicated that ophiobolin O could bind to GSK3β, and GSK3β knockdown abolished cyclin D1 degradation and G1 phase arrest. Pre-treatment with phosphatase inhibitor sodium or thovanadate halted dephosphorylation of AKT and GSK3β, and blocked ophiobolin O-induced G1 phase arrest. These data suggest that ophiobolin O may induce G1 arrest in MCF-7 cells through interaction with AKT/GSK3β/cyclin D1 signaling. In vivo, ophiobolin O suppressed tumor growth and showed little toxicity in mouse xenograft models. Overall, these findings provide theoretical basis for the therapeutic use of ophiobolin O.http://www.mdpi.com/1660-3397/13/1/431ophiobolin OG1 arrestAKT/GSK3β/cyclin D1 signaling |
| spellingShingle | Cuiting Lv Wenxing Qin Tonghan Zhu Shanjian Wei Kui Hong Weiming Zhu Ruohua Chen Caiguo Huang Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling Marine Drugs ophiobolin O G1 arrest AKT/GSK3β/cyclin D1 signaling |
| title | Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling |
| title_full | Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling |
| title_fullStr | Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling |
| title_full_unstemmed | Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling |
| title_short | Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling |
| title_sort | ophiobolin o isolated from aspergillus ustus induces g1 arrest of mcf 7 cells through interaction with akt gsk3β cyclin d1 signaling |
| topic | ophiobolin O G1 arrest AKT/GSK3β/cyclin D1 signaling |
| url | http://www.mdpi.com/1660-3397/13/1/431 |
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