Pro-apoptotic mechanisms of action of a novel vitamin E analog (alpha-TEA) and a naturally occurring form of vitamin E (delta-tocotrienol) in MDA-MB-435 human breast cancer cells.

Abstract

Vitamin E derivative, RRR-alpha-tocopheryl succinate (vitamin E succinate, VES), is a potent pro-apoptotic agent, inducing apoptosis by restoring both transforming growth factor-beta (TGF-beta) and Fas (CD95) apoptotic signaling pathways that contribute to the activation of c-Jun N-terminal kinase (JNK)-mediated apoptosis. Objectives of these studies were to characterize signaling events involved in the pro-apoptotic actions of a naturally occurring form of vitamin E, delta-tocotrienol, and a novel vitamin E analog, alpha-tocopherol ether acetic acid analog [alpha-TEA; 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxyacetic acid]. Like VES, alpha-TEA and delta-tocotrienol induced estrogen-nonresponsive MDA-MB-435 and estrogen-responsive MCF-7 human breast cancer cells to undergo high levels of apoptosis in a concentration- and time-dependent fashion. Like VES, the two compounds induced either no or lower levels of apoptosis in normal human mammary epithelial cells and immortalized but nontumorigenic human MCF-10A cells. The pro-apoptotic mechanisms triggered by the structurally distinct alpha-TEA and delta-tocotrienol were identical to those previously reported for VES, that is, alpha-TEA- and delta-tocotrienol-induced apoptosis involved up-regulation of TGF-beta receptor II expression and TGF-beta-, Fas- and JNK-signaling pathways. These data provide a better understanding of the anticancer actions of a dietary form of vitamin E (delta-tocotrienol) and a novel nonhydrolyzable vitamin E analog (alpha-TEA).

• Authors: Ming-Chieh Shun, Weiping Yu, Abdul Gapor, Rachel Parsons, Jeffrey Atkinson, Bob G Sanders, Kimberly Kline
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 48 Issue 1 Pg. 95-105 ( 2004) ISSN: 0163-5581 [Print] United States
• PMID: 15203383 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2004 Lawrence Erlbaum Associates, Inc.

Chemical References

• Anticarcinogenic Agents
• Receptors, Transforming Growth Factor beta
• fas Receptor
• Vitamin E
• tocotrienol, delta
• 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid
• Tocopherols

Topics

• Anticarcinogenic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (drug therapy, prevention & control)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Receptors, Transforming Growth Factor beta (drug effects, metabolism)
• Signal Transduction (drug effects)
• Tocopherols
• Vitamin E (analogs & derivatives, pharmacology)
• fas Receptor (drug effects, metabolism)