School of Food Science and Engineering, Harbin Institute of Technology, Harbin, 150090, P.R. China; Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, 150081, P.R. China.
J Nutr Biochem. 2012 Jul;23(7):800-7. doi: 10.1016/j.jnutbio.2011.04.003. Epub 2011 Aug 17.
γ-Tocotrienol, a major component of the tocotrienol-rich fraction of palm oil, has been suggested to have antioxidant and anticancer activity as well as potent chemopreventive effects on tumor cells. In this study, the mechanisms underlying γ-tocotrienol-mediated growth inhibition of human carcinoma HT-29 cells were further investigated, especially in correlation with the involvement of β-catenin/T-cell factor (Tcf) signaling pathway. We found that γ-tocotrienol could strongly suppress the transcriptional activity of β-catenin/Tcf signaling pathway in HT-29 cells. γ-Tocotrienol inhibited the expression level of total β-catenin protein but did not significantly affect the phosphorylated β-catenin level. Meanwhile, γ-tocotrienol down-regulated the protein level of nuclear β-catenin and induced its redistribution to cell membrane. Furthermore, γ-tocotrienol suppressed the expression of downstream target genes such as c-myc, cyclin D1 and survivin. The results demonstrated that γ-tocotrienol-inhibited growth and -induced apoptosis in HT-29 cells were accompanied by significant inhibition of β-catenin/Tcf signaling. Blocking the expression of β-catenin with small interfering RNA significantly suppressed the ability of γ-tocotrienol to reduce viability and induce apoptosis in HT-29 cells. Thus, our data suggested that γ-tocotrienol exerts its anticancer activity through β-catenin/Tcf signaling, and β-catenin is a target for γ-tocotrienol in the Wnt/β-catenin signaling pathway.
γ-生育三烯酚是富含生育三烯酚的棕榈油的主要成分，已被证实具有抗氧化和抗癌活性，以及对肿瘤细胞有很强的化学预防作用。在这项研究中，进一步研究了γ-生育三烯酚抑制人结肠癌 HT-29 细胞生长的机制，特别是与β-连环蛋白/T 细胞因子（Tcf）信号通路的参与相关的机制。我们发现，γ-生育三烯酚能强烈抑制 HT-29 细胞中β-连环蛋白/Tcf 信号通路的转录活性。γ-生育三烯酚抑制总β-连环蛋白蛋白的表达水平，但对磷酸化β-连环蛋白水平没有显著影响。同时，γ-生育三烯酚下调核β-连环蛋白的蛋白水平，并诱导其重新分布到细胞膜。此外，γ-生育三烯酚抑制下游靶基因如 c-myc、cyclin D1 和 survivin 的表达。结果表明，γ-生育三烯酚抑制 HT-29 细胞生长和诱导细胞凋亡伴随着β-连环蛋白/Tcf 信号的显著抑制。用小干扰 RNA 阻断β-连环蛋白的表达显著抑制了 γ-生育三烯酚降低 HT-29 细胞活力和诱导细胞凋亡的能力。因此，我们的数据表明，γ-生育三烯酚通过β-连环蛋白/Tcf 信号发挥其抗癌活性，β-连环蛋白是 Wnt/β-连环蛋白信号通路中γ-生育三烯酚的靶标。
