The molecular mechanisms of Tanshinone IIA on the apoptosis and arrest of human esophageal carcinoma cells

Biomed Res Int. 2014:2014:582730. doi: 10.1155/2014/582730. Epub 2014 Apr 15.

Abstract

Objective: To explore the possible mechanisms of Tanshinone IIA (TanIIA) on esophageal carcinoma cell lines.

Methods: Two human esophageal carcinoma cell lines (EC-1 cells and ECa-109 cells) were treated with different concentrations of TanIIA. Cell proliferation was measured by CCK-8, colony-forming efficiency was calculated, cell cycle and apoptosis were measured, and changes in cell cycle- and apoptosis-related gene expression were measured by Western blotting.

Results: The CCK-8 and colony formation assay indicated that TanIIA inhibited the cell proliferation of human esophageal cancer cells (IC50 below 1 μg/mL) at 48 h. Hoechst 33258 and flow cytometry showed that TanIIA induced apoptosis in both esophageal cancer cell lines. Flow cytometry showed that TanIIA arrested cell cycle in S phase and G2/M phase. Western blotting analysis showed that Akt1 and its phosphorylation were inhibited, the Bax/Bcl-2 ratio increased, and both caspase-9 and caspase-3 were activated after treatment with 1.3 μg/mL TanIIA at 48 h. Meanwhile, p53 and p21 protein levels increased, whereas cyclin B1, CDC2, and CDC2 phosphorylation were inhibited.

Conclusion: TanIIA inhibits the growth of esophageal cancer cells and induces apoptosis in a time-dependent and concentration-dependent manner, possibly by affecting cell cycle- and apoptosis-related signaling pathways.

MeSH terms

  • Abietanes / chemistry
  • Abietanes / pharmacology*
  • Abietanes / therapeutic use
  • Apoptosis / drug effects*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / pathology*
  • G2 Phase / drug effects
  • Humans
  • Mitosis / drug effects
  • Neoplasm Proteins / metabolism
  • Signal Transduction / drug effects

Substances

  • Abietanes
  • Neoplasm Proteins
  • tanshinone