Identification of a new cyathane diterpene that induces mitochondrial and autophagy-dependent apoptosis and shows a potent in vivo anti-colorectal cancer activity----中国科学院微生物研究所

科研成果

论文题目:	Identification of a new cyathane diterpene that induces mitochondrial and autophagy-dependent apoptosis and shows a potent in vivo anti-colorectal cancer activity
作者:	He Luwei, Han Junjie, Li Baowei, Huang Li, Ma Ke, Chen Quan, Liu Xinzhong, Bao Li, and Liu Hongwei*.
联系作者:
刊物名称:	Eur J Med Chem
期:
卷:	111
页:	183-92
年份:	2016
影响因子:	3.946
论文下载:	http://www.sciencedirect.com/science/article/pii/S0223523416300642
摘要:	Diterpenes has been reported to possess multiple bioactivities consisting of anti-microbial and anti-inflammatory properties. This study reveals a new cyathane-type diterpene (cyathin Q) from the culture of the fungus Cyathus africanus by bioactivity-guided separation. The structure of cyathin Q was determined based on spectroscopic measurements (NMR and MS). The bioactivity evaluation shows that cyathin Q has a strong anticancer activity against HCT116 cells and Bax-deficient HCT116 in vitro and in vivo. This compound induced hallmarks of apoptotic events in HCT116 cells, including caspase activation, cytochrome c release, poly (ADP-ribose) polymerase (PARP) cleavage, and depolarization of the mitochondrial inner transmembrane potential. This process is accompanied with the increased mitochondrial ROS, down-regulation of Bcl-2 protein, and up-regulation of Bim protein. We also observed the cleavage of autophagy-related protein ATG5 in cyathin Q-induced apoptosis. Taken together, our study identified a new fungal diterpene that exhibited anticancer activity via induction of mitochondria and autophagy-dependent apoptosis in HCT116 cells.