ArticleOncogene2005
2-Methoxyestradiol-induced apoptosis in human leukemia cells proceeds through a reactive oxygen species and Akt-dependent process.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 104 citations in OpenAlex.
- Article
- A Novel Aniline Derivative fromInternational journal of molecular sciences · 2023Article
- Self-Nanoemulsifying Drug Delivery System of 2-Methoxyestradiol Exhibits Enhanced Anti-Proliferative and Pro-Apoptotic Activities in MCF-7 Breast Cancer Cells.Life (Basel, Switzerland) · 2022Article
- Capsanthin-Loaded Micelles: Preparation, Characterization andFood technology and biotechnology · 2022Article
- Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?Antioxidants (Basel, Switzerland) · 2022Review
- RETRACTED: Polyphyllin I Promotes Autophagic Cell Death and Apoptosis of Colon Cancer Cells via the ROS-Inhibited AKT/mTOR Pathway.International journal of molecular sciences · 2022Article
- A preliminary evaluation of oxidative stress in patients with gastric cancer before chemotherapy.Archives of medical science : AMS · 2022Article
- Redox Control in Acute Lymphoblastic Leukemia: From Physiology to Pathology and Therapeutic Opportunities.Cells · 2021Review
- Oxidative resistance of leukemic stem cells and oxidative damage to hematopoietic stem cells under pro-oxidative therapy.Cell death & disease · 2020Review
- Celastrol induces ROS-mediated apoptosis via directly targeting peroxiredoxin-2 in gastric cancer cells.Theranostics · 2020Article
- ROS-mediated activation and mitochondrial translocation of CaMKII contributes to Drp1-dependent mitochondrial fission and apoptosis in triple-negative breast cancer cells by isorhamnetin and chloroquine.Journal of experimental & clinical cancer research : CR · 2019Article
- Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells.Scientific reports · 2018Article
- Reactive oxygen species in haematopoiesis: leukaemic cells take a walk on the wild side.Journal of experimental & clinical cancer research : CR · 2018Review
- Characterization of potent and selective iodonium-class inhibitors of NADPH oxidases.Biochemical pharmacology · 2017Article
- Effect of 2-methoxyestradiol on SK-LMS-1 uterine leiomyosarcoma cells.Oncology letters · 2017Article
- Synergistic antitumor activity of rapamycin and EF24 via increasing ROS for the treatment of gastric cancer.Redox biology · 2016Article
- DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol.Oncotarget · 2015Article
- Tyrosine kinase inhibition in leukemia induces an altered metabolic state sensitive to mitochondrial perturbations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- The Bruton tyrosine kinase (BTK) inhibitor PCI-32765 synergistically increases proteasome inhibitor activity in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells sensitive or resistant to bortezomib.British journal of haematology · 2013Article
- PLK1 inhibitors synergistically potentiate HDAC inhibitor lethality in imatinib mesylate-sensitive or -resistant BCR/ABL+ leukemia cells in vitro and in vivo.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The effects of 2-Methoxyestradiol (2ME)-induced apoptosis was examined in human leukemia cells (U937 and Jurkat) in relation to mitochondrial injury, oxidative damage, and perturbations in signaling pathways. 2ME induced apoptosis in these cells in a dose-dependent manner associated with release of mitochondrial proteins (cytochrome c, AIF), generation of reactive oxygen species (ROS), downregulation of Mcl-1 and XIAP, and inactivation (dephosphorylation) of Akt accompanied by activation of JNK. In these cells, enforced activation of Akt by a constitutively active myristolated Akt construct prevented 2ME-mediated mitochondrial injury, XIAP and Mcl-1 downregulation, JNK activation, and apoptosis, but not ROS generation. Conversely, 2ME lethality was potentiated by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Furthermore, in U937 cells, the hydrogen peroxide scavenger catalase and a superoxide dismutase (SOD) mimetic, TBAP, blocked these events, as well as Akt inactivation. Interruption of the JNK pathway by pharmacologic or genetic (e.g. siRNA) means attenuated 2ME-induced mitochondrial injury, XIAP and Mcl-1 downregulation, and apoptosis. Collectively, these findings suggest a hierarchical model of 2ME-related apoptosis induction in human leukemia cells in which 2ME-induced oxidative injury represents a primary event resulting in Akt inactivation, leading, in turn, to JNK activation, and culminating in XIAP and Mcl-1 downregulation, mitochondrial injury, and apoptosis. They also suggest that in human leukemia cells, the Akt pathway plays a critical role in mediating the response to oxidative stress induced by 2ME.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.