TNFalpha potentiates 2-methoxyestradiol-induced mitochondrial death pathway.
Ewing sarcoma cells are resistant to TNFalpha-induced cell death and this resistance results from the activation of the transcription factor NF-kappaB. Here, we investigated whether NF-kappaB activation interferes with 2-Me-induced cell death signaling in Ewing sarcoma cells and we examined the effect of treatment of these cells with 2-Me either alone or in combination with TNFalpha. Our results show that TNFa cooperates with 2-Me to induce apoptosis in Ewing tumor cells through mitochondrial cell death signaling. These results suggest that the use of TNFalpha in combination with 2-Me may be beneficial for Ewing tumor treatment.
Djavaheri-Mergny
Mojgan
M
INSERM U365, Institut Curie, 26 rue d'Ulm, 75248 Cedex 05 Paris, France. Mergny@vjf.inserm.fr
Wietzerbin
Juana
J
Rouillard
Dany
D
Besançon
Françoise
F
D000077584:2-Methoxyestradiol; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D012512:Sarcoma, Ewing; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D000077584:2-Methoxyestradiol