title: Geridonin, a novel derivative of oridonin, inhibits proliferation of MGC 803 cells both in vitro and in vivo through elevating the intracellular ROS.
abstract: OBJECTIVE
  To study the antitumour activity of a novel derivative of oridonin named geridonin in vitro and in vivo.
  
  
  METHODS
  MTT and colony formation assay were used to test the cytotoxicity of geridonin; apoptosis, cell cycle arrest and the levels of reactive oxygen species were measured by flow cytometry; JC-1 staining assay was used to examine the mitochondrial membrane potential; the MGC 803 xenograft model was established to evaluate the antitumour effect of geridonin in vivo; H&E staining was performed for the histological analysis.
  
  
  RESULTS
  In vitro, geridonin remarkably inhibited proliferation of gastrointestinal cancer cells including oesophageal, gastric, liver and colon cancers. On oesophageal, gastric cancer cells, geridonin displayed strong cytotoxicity than that of oridonin. In gastric cancer MGC 803 cells, geridonin triggered apoptosis through the mitochondrial pathway depending on caspase. In addition, geridonin sharply reduced the formation of cell colony, increased the intracellular levels of ROS and induced cell cycle arrest at G2/M phase. In vivo, geridonin delayed the growth of MGC 803 xenograft in athymic mice without obvious loss of bodyweight.
  
  
  CONCLUSIONS
  The novel derivative of oridonin, geridonin, inhibited the growth of human gastric cancer cells MGC 803 both in vitro and in vivo mainly via triggering apoptosis depending on elevating intracellular level of ROS.
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Sai-Qi
authors.initials: SQ
authors.lastname: Wang
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Wang
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Dong-Xiao
authors.initials: DX
authors.lastname: Yang
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Chuan-Jin
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Li
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Hong-Ge
authors.initials: HG
authors.lastname: Shi
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D045786:Diterpenes, Kaurane; D017382:Reactive Oxygen Species; C000620433:geridonin
keywords: 
  ROS
  ; apoptosis; cell cycle; gastric cancer; geridonin