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The α-tocopherol derivative ESeroS-GS induces cell death and inhibits cell motility of breast cancer cells through the regulation of energy metabolism.

Abstract
Cancer cells are known to exhibit different hallmarks compared with normal cells. Therefore, targeting these features may improve the response to cancer therapy. In this study, we provided direct evidence that the α-tocopherol derivative ESeroS-GS inhibited the viability, migration, and invasion of breast cancer cells. ESeroS-GS induced cell death in different cancer cells in a dose-dependent manner but showed no significant effects on MCF-10A mammary epithelial cells. Although the ESeroS-GS-induced cell death in MDA-MB-231 breast cancer cells was accompanied with the generation of reactive oxygen species and the down regulation of mitochondrial membrane potential (MMP), no such effect on reactive oxygen species and MMP was seen in MCF-10A cells. Further studies indicated that ESeroS-GS down-regulated the expression of hexokinase II, SDH B, UQCRC2 and COX II in MDA-MB-231 cells but not in MCF-10A cells. The down-regulation of these enzymes accounts for the decreased oxidative phosphorylation (OXPHOS) and glycolysis in MDA-MB-231 cells upon ESeroS-GS treatment. We also found that sub-toxic concentration of ESeroS-GS treatment resulted in the impairment of F-actin cytoskeleton assembly and the consequently decreased migratory and invasive ability of MDA-MB-231 cells, which might be due to the inhibition of cellular energy metabolism. These results indicate that ESeroS-GS shows potential to become a novel anti-cancer agent by targeting the energy metabolism of cancer cells.
AuthorsLijing Zhao, Xingyu Zhao, Kai Zhao, Peng Wei, Yi Fang, Fenglin Zhang, Bo Zhang, Kazumi Ogata, Akitane Mori, Taotao Wei
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 745 Pg. 98-107 (Dec 15 2014) ISSN: 1879-0712 [Electronic] Netherlands
PMID25446928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Antioxidants
  • Benzopyrans
  • Chromans
  • Indoles
  • Reactive Oxygen Species
  • glutamyl-(2-(((3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl)oxy)carbonyl)-3-((2-(1H-indol-3-yl)ethyl)amino)-3-oxopropyl)-cysteinyl-glycine sodium salt
  • Vitamin E
  • potassium ascorbyl tocopheryl phosphate
  • Adenosine Triphosphate
  • alpha-Tocopherol
  • Ascorbic Acid
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
Topics
  • Adenosine Triphosphate (biosynthesis)
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacology)
  • Antioxidants (pharmacology)
  • Ascorbic Acid (analogs & derivatives, pharmacology)
  • Benzopyrans (administration & dosage, pharmacology)
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Cell Survival (drug effects)
  • Chromans (pharmacology)
  • Dose-Response Relationship, Drug
  • Energy Metabolism (drug effects)
  • Female
  • Glycolysis (drug effects)
  • HeLa Cells
  • Humans
  • Indoles (administration & dosage, pharmacology)
  • Mammary Glands, Human (cytology, drug effects, metabolism)
  • Membrane Potential, Mitochondrial (drug effects)
  • Mice
  • NIH 3T3 Cells
  • Neoplasm Invasiveness (pathology)
  • Oxidative Phosphorylation (drug effects)
  • Reactive Oxygen Species (metabolism)
  • Vitamin E (analogs & derivatives, pharmacology)
  • alpha-Tocopherol (administration & dosage, analogs & derivatives, pharmacology)

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