Tocotrienols activity in MCF-7 breast cancer cells: Involvement of ERβ signal transduction

✍ Scribed by Raffaella Comitato; Guido Leoni; Raffaella Canali; Roberto Ambra; Kalanithi Nesaretnam; Fabio Virgili

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 349 KB
• Volume: 54
• Category: Article
• ISSN: 1613-4125
• DOI: 10.1002/mnfr.200900383

✦ Synopsis

Abstract

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 (ERβ) signalling. In this study, we report that, in MCF‐7 breast cancer cell, expressing both ERα and ERβ, PTRF treatment increases ERβ nuclear translocation, as demonstrated by immunofluorescence experiments and significantly inhibits ERα 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 γ‐TT with respect to α‐TT. Our data suggest a novel potential molecular mechanism for TTs activity.