title: Dihydrotanshinone induces apoptosis of SGC7901 and MGC803 cells via activation of JNK and p38 signalling pathways.
abstract: BACKGROUND
  Dihydrotanshinone (DHT), a natural compound from Salvia miltiorrhiza Bunge (Lamiaceae), showed higher cytotoxic potential compared with other tanshinones. Its effect and mechanism on gastric cancer have not been investigated.
  
  
  OBJECTIVE
  This study evaluates the effects of DHT on cell proliferation and apoptosis on gastric cancer cells, and elucidates its molecular mechanisms.
  
  
  METHODS
  Human gastric cancer MGC803 and SGC7901 cells were treated with various concentrations of DHT (0-15 μM) for 24 and 48 h, and cell growth was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cell apoptosis was analysed by flow cytometry and DAPI staining. Western blots were performed to investigate changes in the level of apoptosis related genes in gastric cancer cell.
  
  
  RESULTS
  DHT exhibited obvious inhibition of the survival of gastric cancer cells. The IC50values in SGC7901 and MGC803 cells were 9.14 and 5.39 μM for 24 h, respectively. Cells treated with 6 μM DHT resulted in 41.3% and 35.4% apoptotic cell fractions in SGC7901 and MGC803 cells, respectively, significantly higher than that of the control. Hallmarks of apoptosis were observed in gastric cancer cells after DHT exposure. DHT enhanced the expression levels of cleaved caspase-3, caspase-9 and poly-ADP-ribose polymerases. Furthermore, DHT increased the phosphorylation of JNK and p38 in SGC7901 and MGC803 cells.
  
  
  CONCLUSIONS
  DHT induced growth inhibition and apoptosis of gastric cancer cells, involving activation of caspase proteins and the JNK/p38 signaling pathway. The results indicated that DHT has a promising chemotherapeutic potential for human gastric cancer.
authors.affiliation: a College of Pharmaceutical Science , Zhejiang Chinese Medical University , Hangzhou , P.R. China.
authors.forename: Rubin
authors.initials: R
authors.lastname: Cheng
authors.affiliation: a College of Pharmaceutical Science , Zhejiang Chinese Medical University , Hangzhou , P.R. China.
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Chen
authors.affiliation: a College of Pharmaceutical Science , Zhejiang Chinese Medical University , Hangzhou , P.R. China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b The First Affiliated Hospital, Zhejiang Chinese Medical University , Hangzhou , P.R. China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Ge
authors.affiliation: a College of Pharmaceutical Science , Zhejiang Chinese Medical University , Hangzhou , P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: c College of Basic Medical Science , Zhejiang Chinese Medical University , Hangzhou , P.R. China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Zhang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C021751:tanshinone
keywords: Antitumour activity; gastric cancer prevention; natural product; tanshinone extracts