title: [Jaridonin, a new diterpenoid from Isodon rubescens, induces cell cycle arrest in gastric cancer cells through activating ataxia telangiectasia mutated kinase].
abstract: OBJECTIVE
  To study the effects of Jaridonin, a novel diterpenoid from isodon rubescens, on the cell cycle of human gastric cancer cells and its molecular mechanism of action.
  
  
  METHODS
  Flow cytometry was used to analyze the cell cycle distribution and expression of ataxia telangiectasia mutated kinase (ATM) after Jaridonin treatment. Western blot was performed to detect the expression of cell cycle-related proteins.
  
  
  RESULTS
  The results of flow cytometry showed that the percentages of MGC-803 cells in G(2)/M phase at 6 hours after 0, 10, 20 μmol/L Jaridonin-treatment were (10.8±2.2)%, (18.2±2.5)%, (27.3±3.2)%, respectively; those at 12 hours after Jaridonin-treatment were (12.0±1.5)%, (24.1±2.0)% and (39.7±5.2)%, respectively, indicating a G2/M phase arrest of MGC-803 cells was resulted in a time- and dose-dependent manner. The expressions of ATM, Chk1, Chk2, phosphorylated Cdc2 and CDK2 were up-regulated in the MGC-803 cells after Jaridonin treatment, while the levels of Cdc2 and CDK2 were decreased. KU-55933, an inhibitor of ATM, reversed the expression of relevant proteins and G(2)/M phase arrest induced by Jaridonin.
  
  
  CONCLUSIONS
  Jaridonin can significantly induce G(2)/M arrest in gastric cancer MGC-803 cells. Its mechanism may be related to the activation of ATM and Chk1/2, and inactivation of Cdc2 and CDK2 phosphorylation.
authors.affiliation: Laboratory of Clinical Pharmacology, People's Hospital, Zhengzhou University, Zhengzhou 450003, China.
authors.forename: Y C
authors.initials: YC
authors.lastname: Ma
authors.affiliation: School of Food Science and Engineering, Henan University of Animal Husbandry and Economy, Zhengzhou 450011, China.
authors.forename: N
authors.initials: N
authors.lastname: Su
authors.affiliation: Laboratory of Clinical Pharmacology, People's Hospital, Zhengzhou University, Zhengzhou 450003, China.
authors.forename: N M
authors.initials: NM
authors.lastname: Zhao
authors.affiliation: Laboratory of Clinical Pharmacology, People's Hospital, Zhengzhou University, Zhengzhou 450003, China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Li
authors.affiliation: Laboratory of Clinical Pharmacology, People's Hospital, Zhengzhou University, Zhengzhou 450003, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Laboratory of Clinical Pharmacology, People's Hospital, Zhengzhou University, Zhengzhou 450003, China.
authors.forename: H W
authors.initials: HW
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, New Drug Research& Development Center, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: H M
authors.initials: HM
authors.lastname: Liu
authors.affiliation: Laboratory of Clinical Pharmacology, People's Hospital, Zhengzhou University, Zhengzhou 450003, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Qin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001260:Ataxia Telangiectasia; D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism*; D045744:Cell Line, Tumor; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006801:Humans; D037602:Isodon / Q000737:chemistry*; D009025:Morpholines / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation; D011753:Pyrones / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: C495818:2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one; D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D045786:Diterpenes, Kaurane; D009025:Morpholines; D009363:Neoplasm Proteins; D011753:Pyrones; C587044:jaridonin; D064007:Ataxia Telangiectasia Mutated Proteins