title: γ-Tocotrienol inhibits cell viability through suppression of β-catenin/Tcf signaling in human colon carcinoma HT-29 cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Weili
authors.initials: W
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Du
authors.forename: Yonghuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Wenguang
authors.initials: W
authors.lastname: Sun
authors.forename: Bingqing
authors.initials: B
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D019073:HT29 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D000073878:Palm Oil; D010766:Phosphorylation; D010936:Plant Extracts; D010938:Plant Oils / Q000737:chemistry; D000077022:Survivin; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; C495270:CTNNB1 protein, human; D002839:Chromans; D051034:Inhibitor of Apoptosis Proteins; D010936:Plant Extracts; D010938:Plant Oils; D000077022:Survivin; D051820:TCF Transcription Factors; D051176:beta Catenin; D019938:Cyclin D1; D014810:Vitamin E; C013649:plastochromanol 8; D000073878:Palm Oil