title: Schizandra chinensis extracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway.
abstract: BACKGROUND
  Schizandra chinensis Baill (Magnoliaceae) fruit extract (SCE) is considered a traditional herbal medicine for the treatment and alleviation of various diseases. Gastric cancer is the second most common cause of cancer-related death worldwide, and the first most common in Korea.
  
  
  OBJECTIVE
  This study investigates the mechanism of SCE-induced apoptosis in AGS human gastric cancer cells.
  
  
  METHODS
  SCE concentrations from 100 to 400 µg/ml were used. Cell viabilities were determined using MTT assay. Members of the Bcl-2 family and Bax were detected by Western blotting. RT-PCR was performed to measure the expression level of the Fas/FasL pro-apoptotic genes.
  
  
  RESULTS
  SCE inhibited the proliferation AGS cells for 24 or 72 h (inhibition by 3.1% ± 5.2% at 100 µg/ml and 87.3% ± 7.6% at 400 µg/ml at 24 h and by 40.2% ± 5.3% 100 µg/ml and 95.3% ± 1.3% 400 µg/ml at 72 h) and increased the sub-G1 phase (25.3% ± 5.2% at 100 µg/ml and 370.2% ± 7.2% at 400 µg/ml) and the mitochondrial membrane depolarization (11.2% ± 2.1% at 100 µg/ml and 311.5% ± 6.1% at 400 µg/ml). The SCE-induced apoptotic cell death showed the down-regulation of Bcl-2, but up-regulation of Bax. Subsequently, SCE increased the expression level of Fas/FasL, activated caspase-9 and -3, and increased reactive oxygen species generation. Also, JNK II inhibitor or a p38 MAPK inhibitor inhibited SCE-induced cell death.
  
  
  CONCLUSIONS
  These results indicate that SCE might be an effective chemotherapeutic for the treatment of human gastric cancer.
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine , Yangsan , Republic of Korea .
authors.forename: Hyun Sul
authors.initials: HS
authors.lastname: Kim
authors.forename: Jae Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Geum San
authors.initials: GS
authors.lastname: Lee
authors.forename: Hyung Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005638:Fruit / Q000737:chemistry; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D032141:Schisandra / Q000737:chemistry*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: AGS cell; Schizandra chinensis fruit extract; apoptosis; gastric cancer