γ-Tocotrienol inhibits cell viability through suppression of β-catenin/Tcf signaling in human colon carcinoma HT-29 cells

gamma-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 gamma-tocotrienol-mediated growth inhibition of human carcinoma HT-29 cells were further investigated, especially in correlation with the involvement of beta-catenin/T-cell factor (Tcf) signaling pathway. We found that gamma-tocotrienol could strongly suppress the transcriptional activity of beta-catenin/Tcf signaling pathway in HT-29 cells. gamma-Tocotrienol inhibited the expression level of total beta-catenin protein but did not significantly affect the phosphorylated beta-catenin level. Meanwhile, gamma-tocotrienol down-regulated the protein level of nuclear beta-catenin and induced its redistribution to cell membrane. Furthermore, gamma-tocotrienol suppressed the expression of downstream target genes such as c-myc, cyclin D1 and survivin. The results demonstrated that gamma-tocotrienol-inhibited growth and -induced apoptosis in HT-29 cells were accompanied by significant inhibition of beta-cateninfl-cf signaling. Blocking the expression of beta-catenin with small interfering RNA significantly suppressed the ability of gamma-tocotrienol to reduce viability and induce apoptosis in HT-29 cells. Thus, our data suggested that gamma-tocotrienol exerts its anticancer activity through beta-cateninffcf signaling, and beta-catenin is a target for gamma-tocotrienol in the Wnt/beta-catenin signaling pathway. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.