ArticleAntioxidants (Basel, Switzerland)2020
Targeting the MAPK/ERK and PI3K/AKT Signaling Pathways Affects NRF2, Trx and GSH Antioxidant Systems in Leukemia Cells.
Article in Antioxidants (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
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- The Follicular Immune Checkpoint: PD-1/PD-L1 and Immune Tolerance in Oocyte Competence and IVF Failure.International journal of molecular sciences · 2026Review
- Activation of the nucleus nuclear factor erythroid 2-related factor 2ghrelin/growth hormone secretagogue receptor 1a signaling by Yueju pill confers cardioprotective and antidepressant effects.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Margin of Error: The Emerging Role of Field Cancerization in Predicting Recurrence Risk of Ductal Carcinoma In Situ.International journal of molecular sciences · 2026Review
- Article
- Nrf2 as a Molecular Guardian of Redox Balance and Barrier Integrity in IBD.Antioxidants (Basel, Switzerland) · 2025Review
- DBN1‑mediated upregulation of GAB2 facilitates the migration and invasion of T‑cell acute lymphoblastic leukemia cells.Oncology reports · 2025Article
- Therapeutic innovations: targeting ROS production in AML with natural and synthetic compounds.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Excavatolide C has oxidative-stress-dependent antiproliferative and apoptotic effects against breast cancer cells.BMC cancer · 2025Article
- Review
- Ameliorative Effect of N-Acetylcysteine Against 5-Fluorouracil-Induced Cardiotoxicity via Targeting TLR4/NF-κB and Nrf2/HO-1 Pathways.Medicina (Kaunas, Lithuania) · 2025Article
- RIT1 Promotes the Proliferation of Gliomas Through the Regulation of the PI3K/AKT/c-Myc Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Wine- and stir-frying processing of Cuscutae Semen enhance its ability to alleviate oxidative stress and apoptosis via the Keap 1-Nrf2/HO-1 and PI3K/AKT pathways in HBMC complementary medicine and therapies · 2024Article
- Design and In Vitro Activity of Furcellaran/Chitosan Multilayer Microcapsules for the Delivery of Glutathione and Empty Model Multilayer Microcapsules Based on Polysaccharides.Materials (Basel, Switzerland) · 2024Article
- Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells.Molecules (Basel, Switzerland) · 2024Article
- Lnc-CLSTN2-1:1 Promotes Osteosarcoma Progression by Disrupting Redox Balance through PI3K/AKT Signaling Pathway.Journal of Cancer · 2024Article
- Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK-Nrf2-HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells.Open life sciences · 2024Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- Desmoglein 2 Functions as a Receptor for Fatty Acid Binding Protein 4 in Breast Cancer Epithelial Cells.Molecular cancer research : MCR · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The mitogen-activated protein kinase (MAPK)/extracellular signal kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signal transduction pathways have been implicated in the pathogenesis of leukemia. The aim of this study was to investigate the effect of the combination of ERK1/2 inhibitor AZD0364 and PI3K inhibitor ZSTK474 on acute lymphoblastic leukemia (ALL) REH, MOLT-4, acute myeloid leukemia (AML) MOLM-14, and chronic myeloid leukemia (CML) K562 cell lines. To evaluate the interactions of the drugs, cells were treated for 48 h with AZD0364 or ZSTK474 alone and in combination at fixed ratios. The combinatorial effects of both inhibitors were synergistic over a wide range of concentrations in REH, MOLT-4, and MOLM-14 cell lines. However, in K562 cells, the effects were found to be antagonistic. Furthermore, AZD0364 and ZSTK474 significantly decreased both ERK1/2 and AKT activation in REH, MOLT-4, and MOLM-14 cells. The results showed that incubation with both AZD0364 and ZSTK474 inhibited cell viability, increased reactive oxygen species (ROS) production, and induced apoptosis in leukemia cells. We observed that combined treatment with AZD0364 and ZSTK474 affected nuclear factor-κB (NF-κB) and antioxidant protein levels: NF-E2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), thioredoxin (Trx), thioredoxin reductase (TrxR), and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio. These effects were accompanied with decreased antiapoptotic survivin protein level. However, distinct cell line dependent effects were observed. In conclusion, the combination of AZD0364 and ZSTK474 can exert a synergistic anticancer effect in ALL and AML cells, which is associated with the induction of oxidative stress and the involvement of cellular antioxidant defense mechanisms.
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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.