1. Academic Validation
  2. Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission

  • J Nat Prod. 2022 Oct 18. doi: 10.1021/acs.jnatprod.2c00524.
Xiao-Jie Chen 1 2 Qi-Xiao Cui 1 2 3 Guo-Li Wang 1 2 Xiao-Li Li 1 2 Xiao-Lin Zhou 1 2 Hui-Jie Zhao 1 2 Ming-Qian Zhang 1 2 Min-Jing Li 1 2 Xiao-Juan He 4 Qiu-Sheng Zheng 1 2 Yu-Liang Wang 3 Defang Li 1 2 Pan Hong 1 2
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 College of Stomatology, Binzhou Medical University, Yantai 264003, Shandong, People's Republic of China.
  • 4 Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, People's Republic of China.
Abstract

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.

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