PMID- 36256535 OWN - NLM STAT- MEDLINE DCOM- 20221031 LR - 20221107 IS - 1520-6025 (Electronic) IS - 0163-3864 (Linking) VI - 85 IP - 10 DP - 2022 Oct 28 TI - Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission. PG - 2351-2362 LID - 10.1021/acs.jnatprod.2c00524 [doi] AB - Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment. FAU - Chen, Xiao-Jie AU - Chen XJ AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Cui, Qi-Xiao AU - Cui QX AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - College of Stomatology, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Wang, Guo-Li AU - Wang GL AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Li, Xiao-Li AU - Li XL AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Zhou, Xiao-Lin AU - Zhou XL AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Zhao, Hui-Jie AU - Zhao HJ AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Zhang, Ming-Qian AU - Zhang MQ AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Li, Min-Jing AU - Li MJ AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - He, Xiao-Juan AU - He XJ AD - Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, People's Republic of China. FAU - Zheng, Qiu-Sheng AU - Zheng QS AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Wang, Yu-Liang AU - Wang YL AD - College of Stomatology, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Li, Defang AU - Li D AUID- ORCID: 0000-0003-4151-9151 AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. FAU - Hong, Pan AU - Hong P AUID- ORCID: 0000-0001-7262-278X AD - Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. AD - Collaborative Innovation Platform for Modernization and Industrialization of Regional Characteristic Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221018 PL - United States TA - J Nat Prod JT - Journal of natural products JID - 7906882 RN - 80651-76-9 (sanggenone C) RN - EC 2.7.- (Protein Kinases) SB - IM MH - Mice MH - Animals MH - Humans MH - *Mitochondrial Dynamics MH - *Stomach Neoplasms/drug therapy MH - Mice, Nude MH - Protein Kinases/pharmacology MH - Apoptosis MH - Carcinogenesis MH - Cell Proliferation MH - Cell Line, Tumor EDAT- 2022/10/19 06:00 MHDA- 2022/11/01 06:00 CRDT- 2022/10/18 12:32 PHST- 2022/10/19 06:00 [pubmed] PHST- 2022/11/01 06:00 [medline] PHST- 2022/10/18 12:32 [entrez] AID - 10.1021/acs.jnatprod.2c00524 [doi] PST - ppublish SO - J Nat Prod. 2022 Oct 28;85(10):2351-2362. doi: 10.1021/acs.jnatprod.2c00524. Epub 2022 Oct 18.