Alpha-tocopheryl succinate induces cytostasis and apoptosis in osteosarcoma cells: the role of E2F1.
Alpha-tocopheryl succinate (alpha-TOS), a redox-inactive analog of vitamin E, induces cell cycle arrest, differentiation, and triggers apoptosis. We examined the ability of alpha-TOS to induce cytostasis and/or apoptosis in two human osteosarcoma cell lines, which carry wild-type pRb but differ in the p53 status. In the wt-p53 cells, alpha-TOS induced apoptosis, which was associated with p53 activation and enhanced E2F1 expression. Mutant p53 cells failed to undergo apoptosis when challenged with alpha-TOS. The cell growth arrest after alpha-TOS treatment was associated with a reduced expression of E2F1. Knocking down E2F1 rendered the alpha-TOS-sensitive cells rather resistant to the apoptotic stimulus inducing a marked and prolonged cell growth arrest. We conclude that alpha-TOS induces cell growth arrest or apoptosis involving E2F1.
Alleva
Renata
R
Department of Anaesthesiology, Rizzoli Orthopaedic Institute, 40100 Bologna, Italy. renalle@libero.it
Benassi
Maria Serena
MS
Tomasetti
Marco
M
Gellert
Nina
N
Ponticelli
Francesca
F
Borghi
Battista
B
Picci
Piero
P
Neuzil
Jiri
J
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000502:physiology*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D006801:Humans; D012516:Osteosarcoma / Q000473:pathology*; D024505:Tocopherols; D014157:Transcription Factors / Q000502:physiology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D014157:Transcription Factors; D014810:Vitamin E; D024505:Tocopherols