title: 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.
authors.affiliation: Central Laboratory, The First Affiliated Hospital of Harbin Medical University, 23 YouZheng Street, NanGang District, Harbin 150001, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Bi
authors.forename: Jia-Ren
authors.initials: JR
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Hui-Kun
authors.initials: HK
authors.lastname: Liu
authors.forename: Ya-Geng
authors.initials: YG
authors.lastname: Yan
authors.forename: Bing-Qing
authors.initials: BQ
authors.lastname: Chen
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Sun
mesh_terms: D000230:Adenocarcinoma; D002460:Cell Line; D002839:Chromans; D003035:Cobalt / Q000494:pharmacology; D006162:Guanylate Cyclase; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear; D015398:Signal Transduction / Q000187:drug effects; D000071756:Soluble Guanylyl Cyclase; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism* / Q000494:pharmacology; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives
chemical_list: D002839:Chromans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014810:Vitamin E; D003035:Cobalt; C013649:plastochromanol 8; D048052:Mitogen-Activated Protein Kinase 3; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase