ArticleOncogene2003
2-Methoxyestradiol induces apoptosis in Ewing sarcoma cells through mitochondrial hydrogen peroxide production.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 82 citations in OpenAlex.
- 2-Methoxyestradiol and Hydrogen Peroxide as Promising Biomarkers in Parkinson's Disease.Molecular neurobiology · 2024Article
- Methoxychlor induces oxidative stress and impairs early embryonic development in pigs.Frontiers in cell and developmental biology · 2023Article
- Pharmacological and Therapeutic Applications of Esculetin.International journal of molecular sciences · 2022Review
- 2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins.Antioxidants (Basel, Switzerland) · 2022Article
- Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma.Journal of nanobiotechnology · 2021Article
- Free Radicals as a Double-Edged Sword: The Cancer Preventive and Therapeutic Roles of Curcumin.Molecules (Basel, Switzerland) · 2020Review
- Modification of DNA structure by reactive nitrogen species as a result of 2-methoxyestradiol-induced neuronal nitric oxide synthase uncoupling in metastatic osteosarcoma cells.Redox biology · 2020Article
- Understanding of ROS-Inducing Strategy in Anticancer Therapy.Oxidative medicine and cellular longevity · 2019Review
- The Specific Vulnerabilities of Cancer Cells to the Cold Atmospheric Plasma-Stimulated Solutions.Scientific reports · 2017Article
- A bis-sulphamoylated estradiol derivative induces ROS-dependent cell cycle abnormalities and subsequent apoptosis.PloS one · 2017Article
- Neuronal Nitric Oxide Synthase-Mediated Genotoxicity of 2-Methoxyestradiol in Hippocampal HT22 Cell Line.Molecular neurobiology · 2016Article
- DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol.Oncotarget · 2015Article
- Combination treatment with 2-methoxyestradiol overcomes bortezomib resistance of multiple myeloma cells.Experimental & molecular medicine · 2013Article
- Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells.Cancer letters · 2011Article
- Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma.Sarcoma · 2011Article
- A new view of carcinogenesis and an alternative approach to cancer therapy.Molecular medicine (Cambridge, Mass.) · 2010Review
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- Effects of hormone deprivation and 2-methoxyestradiol combination therapy on hormone-dependent prostate cancer in vivo.Neoplasia (New York, N.Y.) · 2005Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Ewing sarcoma is the second most common bone tumor in children and young adults. Despite the advances in therapy, the 5-year survival rate for patients with metastatic disease is poor, indicating the need for alternative treatments. Here, we report that 2-methoxy-estradiol (2-Me), a natural estrogen metabolite, induced a caspase-dependent apoptosis of Ewing sarcoma-derived cells independently of their p53 status. 2-Me-induced apoptosis occurred through the mitochondrial death pathway as evidenced by reduction of the mitochondrial transmembrane potential, cytochrome c release and caspase-9 activation. Treatment of cells with 2-Me resulted in generation of intracellular H(2)O(2), which occurred earlier than caspase-9 activation. The H(2)O(2)-reducing agent Ebselen and the lipid peroxidation inhibitor vitamin E decreased both 2-Me-induced caspase-9 activation and cell death, thus providing evidence for a role of H(2)O(2) and lipid peroxides in the initiation of this process. Rotenone, an inhibitor of the mitochondrial respiratory chain, abolished both apoptosis and H(2)O(2) production, thereby identifying mitochondria as the source of H(2)O(2). Moreover, we observed that treatment of cells with 2-Me or H(2)O(2) induced activation of the c-Jun N-terminal kinase (JNK). Overexpression of a dominant-negative mutant of JNK1 reduced 2-Me-induced apoptosis indicating that JNK participates in this process. Altogether, our results provide evidence that 2-Me triggers apoptosis of Ewing sarcoma cells through induction of a mitochondria redox-dependent mechanism and suggest that this compound or other agents that selectively increase the level of reactive oxygen species may prove useful to the development of novel strategies for treatment of Ewing tumors.
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