Rosmarinic Acid Analogue-11 Induces Apoptosis of Human Gastric Cancer SGC-7901 Cells via the Epidermal Growth Factor Receptor (EGFR)/Akt/Nuclear Factor kappa B (NF-κB) Pathway

Med Sci Monit Basic Res. 2019 Feb 25:25:63-75. doi: 10.12659/MSMBR.913331.

Abstract

BACKGROUND According to the latest statistics from the American Cancer Society, there will be 1.73 million cancer cases and more than 600 000 cancer deaths in the United States in 2018, among which there will be 26 240 new cases of gastric cancer and around 10 800 deaths arising from gastric cancer. The objective of this study was to use RAA-11 to intervene in SGC-7901 cells to understand its effects on cell proliferation and apoptosis, and to explore the apoptosis mechanism. MATERIAL AND METHODS MTT assay was used to detect the survival of human gastric mucosal epithelial GES-1 cells and human gastric cancer SGC-7901 cells. Colony formation assay was used to observe the colony forming ability in SGC-7901 cells. The apoptotic rate of SGC-7901 cells was evaluated by Hoechst33258 staining and flow cytometry. qRT-PCR was used to analyze the epidermal growth factor receptor (EGFR) mRNA expression level in SGC-7901 cells. Western blot was used to examine the expression levels of caspase-3, Bcl-2, BAX, EGFR, Akt, p-Akt, and NF-κB in SGC-7901 cells. RESULTS RAA-11 is capable of inhibiting the proliferation and inducing the apoptosis of SGC-7901 cells in a time- and dose-dependent manner. Western blot showed that the expression levels of caspase-3 and BAX were upregulated, while the expression levels of Bcl-2, EGFR, Akt, p-Akt, and NF-κB in the SGC-7901 cells were downregulated. CONCLUSIONS Apoptosis can be induced in SGC-7901 cells by RAA-11, potentially via the EGFR/Akt/NF-κB pathway, indicating that RAA-11 might be a potent agent for cancer treatment.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cinnamates / chemistry
  • Cinnamates / pharmacology*
  • Depsides / chemistry
  • Depsides / pharmacology*
  • ErbB Receptors / drug effects
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rosmarinic Acid
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy*

Substances

  • Cinnamates
  • Depsides
  • NF-kappa B
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt