Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53-and caspase-3-mediated mechanisms
机构：[1]Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Department of Radiology, Zhong-da Hospital, Medical School, Southeast University, Nanjing, China[3]Department of Rehabilitation, The Affiliated Huai’an Hospital of Xuzhou Medical College and The Second People’s Hospital of Huai’an, Huai’an, China[4]NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research (SIPPR), Institutes of Reproduction and Development, Fudan University, Shanghai, China[5]Department of Gastroenterology, Xinhua Hospital, Shanghai Second Medical University, Shanghai, China
Lysine acetylation has been reported to involve in the pathogenesis of multiple diseases including cancer. In our screening study to identify natural compounds with lysine acetyltransferase inhibitor (KATi) activity, oridonin was found to possess acetyltransferase-inhibitory effects on multiple acetyltransferases including P300, GCN5, Tip60, and pCAF. In gastric cancer cells, oridonin treatment inhibited cell proliferation in a concentration-dependent manner and down-regulated the expression of p53 downstream genes, whereas p53 inhibition by PFT-a reversed the antiproliferative effects of oridonin. Moreover, oridonin treatment induced cell apoptosis, increased the levels of activated caspase-3 and caspase-9, and decreased the mitochondrial membrane potential in gastric cancer cells in a concentration-dependent manner. Caspase-3 inhibition by Ac-DEVD-CHO reversed the proapoptosis effect of oridonin. In conclusion, our study identified oridonin as a novel KATi and demonstrated its tumor suppressive effects in gastric cancer cells at least partially through p53- and caspase-3-mediated mechanisms.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472242, 31300959, 81570549]; Shanghai Municipal Health Bureau Key Disciplines Grant [ZK2015A24]; National Basic Research Program GrantNational Basic Research Program of China [2014CB943104]; Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality [14ZR1431600, 13ZR1435400, 14411973700]; Shanghai Municipal Health Bureau [20134100]
第一作者机构：[1]Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Min Shi,Xiao-Jie Lu,Juan Zhang,et al.Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53-and caspase-3-mediated mechanisms[J].ONCOTARGET.2016,7(16):22623-22631.doi:10.18632/oncotarget.8033.
APA：
Min Shi,Xiao-Jie Lu,Juan Zhang,Hua Diao,Guangming Li...&Yu-Gang Wang.(2016).Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53-and caspase-3-mediated mechanisms.ONCOTARGET,7,(16)
MLA：
Min Shi,et al."Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53-and caspase-3-mediated mechanisms".ONCOTARGET 7..16(2016):22623-22631
医学