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Mar. Drugs 2015, 13(1), 431-443; doi:10.3390/md13010431

Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling

1
Department of Biochemistry and Molecular Biology, College of Basic Medical Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China
2
Teaching Management Department, Yangpu Hospital, Tongji University School of Medicine, 450 Tengyue Road, Shanghai 200090, China
3
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
4
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
5
VIP Medicine Department, Changhai Hospital, Shanghai 200433, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Keith Glaser
Received: 9 May 2014 / Accepted: 26 November 2014 / Published: 16 January 2015
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Abstract

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. View Full-Text
Keywords: ophiobolin O; G1 arrest; AKT/GSK3β/cyclin D1 signaling ophiobolin O; G1 arrest; AKT/GSK3β/cyclin D1 signaling
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lv, C.; Qin, W.; Zhu, T.; Wei, S.; Hong, K.; Zhu, W.; Chen, R.; Huang, C. Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling. Mar. Drugs 2015, 13, 431-443.

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