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gamma-Tocotrienol modulates the paracrine secretion of VEGF induced by cobalt(II) chloride via ERK signaling pathway in gastric adenocarcinoma SGC-7901 cell line.

Abstract
Hypoxia is a common characteristic feature of solid tumors, and carcinoma cells are known to secrete many growth factors. These growth factors, such as vascular endothelial growth factor (VEGF), play a major role in the regulation of tumor angiogenesis and metastasis. In this study, the effect of gamma-tocotrienol, a natural product commonly found in palm oil and rice bran, on the accumulation of HIF-1alpha protein and the paracrine secretion of VEGF in human gastric adenocarcinoma SGC-7901 cell line induced by cobalt(II) chloride (as a hypoxia mimic) was investigated. These results showed that cobalt(II) chloride induced the high expression of VEGF in SGC-7901 cells at dose of 150 micromol/L for 24h. Both basal level and cobalt(II) chloride-induced HIF-1alpha protein accumulation and VEGF paracrine secretion were inhibited in SGC-7901 cells treated with gamma-tocotrienol at 60 micromol/L treatment for 24 h. U0126, a MEK1/2 inhibitor, decreased the expression of HIF-1alpha protein and the paracrine secretion of VEGF under normoxic and hypoxic conditions. In this study, gamma-tocotrienol also significantly inhibited the hypoxia-stimulated expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2). The mechanism seems to involve in inhibiting hypoxia-mediated activation of p-ERK1/2, it leads to a marked decrease in hypoxia-induced HIF-1alpha protein accumulation and VEGF secretion. These data suggest that HIF-1alpha/VEGF could be a promising target for gamma-tocotrienol in an effective method of chemoprevention and chemotherapy in human gastric cancer.
AuthorsSheng Bi, Jia-Ren Liu, Yang Li, Qi Wang, Hui-Kun Liu, Ya-Geng Yan, Bing-Qing Chen, Wen-Guang Sun
JournalToxicology (Toxicology) 2010 Jul-Aug Vol. 274 Issue 1-3 Pg. 27-33 ISSN: 1879-3185 [Electronic] Ireland
PMID20452389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright2010 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Chromans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Vitamin E
  • Cobalt
  • plastochromanol 8
  • Mitogen-Activated Protein Kinase 3
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
Topics
  • Adenocarcinoma
  • Cell Line
  • Chromans
  • Cobalt (pharmacology)
  • Guanylate Cyclase
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit (metabolism, pharmacology)
  • Mitogen-Activated Protein Kinase 3 (metabolism, pharmacology)
  • Neovascularization, Pathologic
  • Phosphorylation
  • Proteins (metabolism, pharmacology)
  • Receptors, Cytoplasmic and Nuclear
  • Signal Transduction (drug effects)
  • Soluble Guanylyl Cyclase
  • Stomach Neoplasms (blood supply, metabolism, pathology)
  • Vascular Endothelial Growth Factor A (biosynthesis, metabolism, pharmacology)
  • Vascular Endothelial Growth Factors (metabolism, pharmacology)
  • Vitamin E (analogs & derivatives)

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