Tocotrienols activity in MCF-7 breast cancer cells: involvement of ERbeta signal transduction

Mol Nutr Food Res. 2010 May;54(5):669-78. doi: 10.1002/mnfr.200900383.


The term Vitamin E is utilized to describe eight molecules, subdivided into two groups, tocopherols and tocotrienols (TTs). It has been shown that specific TTs affect the growth of several lines of tumour cells, and that this activity is not shared by tocopherols. In agreement with these observations, a TTs-rich fraction from palm oil (PTRF) was reported to inhibit proliferation and induce apoptosis in several cancer cells. However, the molecular mechanism involved in TTs activity is still unclear. We have recently proposed that TTs pro-apoptotic activity involves estrogen receptor beta (ERbeta) signalling. In this study, we report that, in MCF-7 breast cancer cell, expressing both ERalpha and ERbeta, PTRF treatment increases ERbeta nuclear translocation, as demonstrated by immunofluorescence experiments and significantly inhibits ERalpha expression (-458.91-fold of change) and complete disappearing of the protein from the nucleus. Moreover, PTRF treatment induces ER-dependent genes expression (macrophage inhibitory cytokine-1, early growth response-1 and Cathepsin D) which is inhibited by the ER inhibitor, ICI 182.780, and induces DNA fragmentation. Finally, cDNA-array experiments suggest that the activation of specific pathways in cells treated with gamma-TT with respect to alpha-TT. Our data suggest a novel potential molecular mechanism for TTs activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Bone Morphogenetic Protein 4 / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / physiopathology
  • Cathepsin D / genetics
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • DNA Primers
  • DNA, Neoplasm / genetics
  • DNA, Single-Stranded / genetics
  • Estrogen Receptor alpha / physiology
  • Estrogen Receptor beta / physiology*
  • Female
  • Growth Differentiation Factor 15 / genetics
  • Humans
  • Signal Transduction
  • Tocopherols / metabolism
  • Tocotrienols / metabolism*


  • Actins
  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • DNA Primers
  • DNA enzyme ED5
  • DNA, Neoplasm
  • DNA, Single-Stranded
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Tocotrienols
  • Cathepsin D
  • Tocopherols