期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 23, 期 1, 页码 93-100出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2010.11.012
关键词
Vitamin E; Tocotrienol; Breast cancer; ER stress; Unfolded protein response (UPR); Apoptosis
资金
- NCI UDC-LCCC [U56]
- UDC Agricultural Experiment Station
- MBRS SCORE
- NSF HBCU-UP
- NATIONAL CANCER INSTITUTE [SC1CA141935] Funding Source: NIH RePORTER
Gamma-tocotrienol (gamma-T3) is a member of the vitamin E family. Tocotrienols (T3s) are powerful antioxidants and possess anticancer, neuroprotective and cholesterol-lowering properties. Tocotrienols inhibit the growth of various cancer cell lines without affecting normal cells. Less is known about the exact mechanisms of action of T3s on cell death and other growth inhibitory pathways. In the present study, we demonstrate that gamma-T3 induces apoptosis in MDA-MB 231 and MCF-7 breast cancer cells as evident by PARP cleavage and caspase-7 activation. Gene expression analysis of MCF-7 cells treated with gamma-T3 revealed alterations in the expression of multiple genes involved in cell growth and proliferation, cell death, cell cycle, cellular development, cellular movement and gene expression. Further analysis of differentially modulated genes using Ingenuity Pathway Analysis software suggested modulation of canonical signal transduction or metabolic pathways such as NRF-2-mediated oxidative stress response, TGF-beta signaling and endoplasmic reticulum (ER) stress response. Analysis of ER-stress-related proteins in MCF-7 and MDA-MB 231 cells treated with gamma-T3 demonstrated activation of PERK and pIRE1 alpha pathway to induce ER stress. Activating transcription factor 3 (ATF3) was identified as the most up-regulated gene (16.8-fold) in response to gamma-T3. Activating transcription factor 3 knockdown using siRNA suggested an essential role of ATF3 in gamma-T3-induced apoptosis. In summary, we demonstrate that gamma-T3 modulates ER stress signaling and have identified ATF3 as a molecular target for gamma-T3 in breast cancer cells. (C) 2012 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据