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TNFalpha potentiates 2-methoxyestradiol-induced mitochondrial death pathway
Mojgan Djavaheri-Mergny1, Juana Wietzerbin, Dany Rouillard
1INSERM U365, Institut Curie, 26 rue d'Ulm, 75248 Cedex 05 Paris, France. Mergny@vjf.inserm.fr
Abstract:
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.
Insights
Ewing sarcoma cells resistant to TNFalpha-induced death can be killed by combining TNFalpha with 2-Me. This combination therapy targets mitochondrial cell death pathways, offering a potential new treatment for Ewing tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Ewing sarcoma cells exhibit resistance to tumor necrosis factor-alpha (TNFalpha)-induced cell death.
- This resistance is attributed to the activation of the transcription factor nuclear factor-kappa B (NF-kappaB).
Purpose of the Study:
- To investigate if NF-kappaB activation affects 2-Me-induced cell death signaling in Ewing sarcoma.
- To evaluate the combined effect of 2-Me and TNFalpha on Ewing sarcoma cells.
Main Methods:
- Treatment of Ewing sarcoma cells with 2-Me alone and in combination with TNFalpha.
- Analysis of cell death signaling pathways, focusing on mitochondrial pathways.
Main Results:
- TNFalpha and 2-Me synergistically induce apoptosis in Ewing sarcoma cells.
- The combination therapy activates mitochondrial cell death signaling pathways.
Conclusions:
- NF-kappaB activation may not completely inhibit 2-Me-induced cell death when combined with TNFalpha.
- Combined treatment with TNFalpha and 2-Me shows promise as a therapeutic strategy for Ewing tumors.
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