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: Weili Xu, Ming Du, Yonghuan Zhao, Qi Wang, Wenguang Sun, Bingqing Chen
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 23 Issue 7 Pg. 800-7 (Jul 2012) ISSN: 1873-4847 [Electronic] United States
• PMID: 21852086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Chemical References

• BIRC5 protein, human
• CTNNB1 protein, human
• Chromans
• Inhibitor of Apoptosis Proteins
• Plant Extracts
• Plant Oils
• Survivin
• TCF Transcription Factors
• beta Catenin
• Cyclin D1
• Vitamin E
• plastochromanol 8
• Palm Oil

Topics

• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Chromans (pharmacology)
• Colon (cytology, drug effects, pathology)
• Colonic Neoplasms (pathology)
• Cyclin D1 (genetics, metabolism)
• Down-Regulation
• HT29 Cells
• Humans
• Inhibitor of Apoptosis Proteins (genetics, metabolism)
• Palm Oil
• Phosphorylation
• Plant Extracts
• Plant Oils (chemistry)
• Survivin
• TCF Transcription Factors (genetics, metabolism)
• Vitamin E (analogs & derivatives, pharmacology)
• Wnt Signaling Pathway (drug effects)
• beta Catenin (genetics, metabolism)