Inhibitory effects of gamma-tocotrienol on invasion and metastasis of human gastric adenocarcinoma SGC-7901 cells

J Nutr Biochem. 2010 Mar;21(3):206-13. doi: 10.1016/j.jnutbio.2008.11.004. Epub 2009 Feb 5.

Abstract

Natural vitamin E is a mixture of two classes of compounds, tocopherols and tocotrienols. Recent research has revealed that tocotrienols, especially gamma-tocotrienol, exhibit not only the same antioxidant ability as tocopherols, but also remarkable anticancer capacity in cancer cell lines. In this study, the invasion and metastatic capacities of gastric adenocarcinoma SGC-7901 cells and the correlation with antimetastasis mechanisms induced by gamma-tocotrienol were explored. The results showed the inhibitory effects of gamma-tocotrienol at doses of 15, 30, 45 and 60 mumol/L for 48 h on cell migration and cell matrigel invasion; activities of matrix metalloproteinase (MMPs) increased in SGC-7901 cells when compared to the control group (P<.05 or P<.01). An increasing trend in the chemotactic responses to fibronectin (FN) in SGC-7901 cells was found in the gamma-tocotrienol treatments. SGC-7901 cell attachment decreased in the gamma-tocotrienol-treated groups in comparison with the control group (P<.01). The mRNA expressions of MMP-2 and MMP-9 showed that gamma-tocotrienol significantly reduced the matrigel invasion capability through down-regulation of the mRNA expressions of MMP-2 and MMP-9 (P<.01), and up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in SGC-7901 cells by treatment with gamma-tocotrienol for 48 h (P<.05). gamma-Tocotrienol also significantly increased the mRNA expression of nm23-H1 in SGC-7901 cells (P<.01). These findings suggest a potential mechanism of gamma-tocotrienol-mediated antitumor metastasis activity and indicate the role of vitamin E as potential chemopreventative agents against gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antineoplastic Agents / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Chemotaxis / drug effects
  • Chromans / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • NM23 Nucleoside Diphosphate Kinases / genetics
  • NM23 Nucleoside Diphosphate Kinases / metabolism
  • Neoplasm Invasiveness / prevention & control*
  • Neoplasm Metastasis / prevention & control*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Time Factors
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Tissue Inhibitor of Metalloproteinases / metabolism
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology

Substances

  • Antineoplastic Agents
  • Chromans
  • NM23 Nucleoside Diphosphate Kinases
  • Protein Isoforms
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases
  • Vitamin E
  • plastochromanol 8
  • NME1 protein, human
  • Matrix Metalloproteinases