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.