Schizandra chinensis extracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

Pharm Biol. 2015 Feb;53(2):212-9. doi: 10.3109/13880209.2014.913297. Epub 2014 Sep 22.

Abstract

Context: 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.

Objectives: This study investigates the mechanism of SCE-induced apoptosis in AGS human gastric cancer cells.

Materials and 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.

Discussion and conclusion: These results indicate that SCE might be an effective chemotherapeutic for the treatment of human gastric cancer.

Keywords: AGS cell; Schizandra chinensis fruit extract; apoptosis; gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Fruit / chemistry
  • Humans
  • MAP Kinase Kinase 4 / metabolism*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • Schisandra / chemistry*
  • Signal Transduction
  • Stomach Neoplasms / pathology
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Plant Extracts
  • Reactive Oxygen Species
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4