%0 Journal Article
%T Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3¦Â/Cyclin D1 Signaling
%A Cuiting Lv
%A Wenxing Qin
%A Tonghan Zhu
%A Shanjian Wei
%A Kui Hong
%A Weiming Zhu
%A Ruohua Chen
%A Caiguo Huang
%J Marine Drugs
%P 431-443
%D 2015
%I MDPI AG
%R 10.3390/md13010431
%X 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 GSK3¦Â, and induced down-regulation of cyclin D1. The inverse docking (INVDOCK) analysis indicated that ophiobolin O could bind to GSK3¦Â, and GSK3¦Â knockdown abolished cyclin D1 degradation and G1 phase arrest. Pre-treatment with phosphatase inhibitor sodium or thovanadate halted dephosphorylation of AKT and GSK3¦Â, 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/GSK3¦Â/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.
%K ophiobolin O
%K G1 arrest
%K AKT/GSK3¦Â/cyclin D1 signaling
%U http://www.mdpi.com/1660-3397/13/1/431