Gamma-tocotrienol-induced apoptosis in human gastric cancer SGC-7901 cells is associated with a suppression in mitogen-activated protein kinase signalling

Br J Nutr. 2008 Jun;99(6):1247-54. doi: 10.1017/S0007114507879128. Epub 2007 Dec 17.


Tocotrienols have been shown to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in tocotrienol-induced apoptosis are still unclear. In the present study, gamma-tocotrienol induced apoptosis in human gastric adenocarcinoma SGC-7901 cell line through down regulation of the extracellular signal-regulated kinase (ERK) signalling pathway. Furthermore, gamma-tocotrienol-induced apoptosis was accompanied by down regulation of Bcl-2, up regulation of Bax, activation of caspase-3, and subsequent poly (ADP-ribose) polymerase cleavage. These results indicated that up or down regulation of Bcl-2 family proteins play a major role in the initiation of gamma-tocotrienol-induced apoptosis as an activator of caspase-3. Gamma-tocotrienol also down regulated the activation of the Raf-ERK signalling pathway, and down regulated c-Myc by decreasing the expressions of Raf-1 and p-ERK1/2 proteins. The results suggest that key regulators in tocotrienol-induced apoptosis may be Bcl-2 families and caspase-3 in SGC-7901 cells through down regulation of the Raf-ERK signalling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Analysis of Variance
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Blotting, Western / methods
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Chromans / therapeutic use*
  • DNA Fragmentation / drug effects
  • Down-Regulation*
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Mitogen-Activated Protein Kinases / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Vitamin E / analogs & derivatives*
  • Vitamin E / therapeutic use
  • bcl-2-Associated X Protein / metabolism


  • Antioxidants
  • BAX protein, human
  • Chromans
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • bcl-2-Associated X Protein
  • Vitamin E
  • plastochromanol 8
  • Poly(ADP-ribose) Polymerases
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases
  • Caspase 3