Elemene Induces Apoptosis of Human Gastric Cancer Cell Line BGC-823 via Extracellular Signal-Regulated Kinase (ERK) 1/2 Signaling Pathway

Med Sci Monit. 2017 Feb 14:23:809-817. doi: 10.12659/msm.903197.

Abstract

BACKGROUND Elemene is extracted from a traditional herbal medicine and is commonly used in the treatment of cancer in China. However, its effect on gastric cancer cells remains unknown. The goal of this study was to investigate its effect on human gastric cancer cells. MATERIAL AND METHODS Human gastric cancer BGC-823 cells and a tumor-bearing mouse model were employed to be divided into 4 groups: control group, elemene group, PD98059 group (an ERK 1/2 signaling pathway inhibitor), and the combined group (elemene plus PD98059). The tumor size, cell proliferation, expression of ERK 1/2 and phosphorylated ERK 1/2 (p-ERK 1/2), Bcl-2 mRNA, and Bax mRNA were measured. Moreover, cell apoptosis was detected and the apoptosis index was calculated. RESULTS Elemene and PD98059 each significantly inhibited the proliferation of gastric cancer cells BGC-823, and their combination showed higher synergistic inhibitory effect (P<0.05). We also found increased expression levels of p-ERK l/2 protein and Bax mRNA, but reduced level of Bcl-2 mRNA expression (P<0.05). Elemene presented higher apoptosis rate in a dose-dependent manner (P<0.05). Furthermore, the injection of elemene decreased the weight of transplanted tumors. CONCLUSIONS Elemene can inhibit the proliferation and induce the apoptosis of gastric cancer cells associated with the ERK 1/2 signaling pathway and expression levels of Bax mRNA and Bcl-2 mRNA.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphorylation
  • Random Allocation
  • Sesquiterpenes / pharmacology*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / pathology

Substances

  • Sesquiterpenes
  • elemene
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3