title: Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53- and caspase-3-mediated mechanisms.
abstract: 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-α 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.
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Radiology, Zhong-da Hospital, Medical School, Southeast University, Nanjing, China.|Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Lu
authors.affiliation: Department of Rehabilitation, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research (SIPPR), Institutes of Reproduction and Development, Fudan University, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Diao
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Second Medical University, Shanghai, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Meng
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Ma
authors.affiliation: NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research (SIPPR), Institutes of Reproduction and Development, Fudan University, Shanghai, China.
authors.forename: Heguo
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D000070837:Lysine Acetyltransferases / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; D004791:Enzyme Inhibitors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C011959:oridonin; D000070837:Lysine Acetyltransferases; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: antiproliferation; apoptosis; gastric cancer; lysine acetyltransferase inhibitor; oridonin