ArticleExperimental hematology & oncology2025
Sarcosine sensitizes lung adenocarcinoma to chemotherapy by dual activation of ferroptosis via PDK4/PDHA1 signaling and NMDAR-mediated iron export.
Article in Experimental hematology & oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed.
- Targeting UXS1-Dependent Glucuronate Detoxification Potentiates Metformin's Anti-Tumor Efficacy in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unveiling DEFB1 as a novel driver and promising therapeutic target in lung adenocarcinoma.Cell death & disease · 2026Article
- MXD4 enhances resistance to KRAS G12C-targeted therapy in lung adenocarcinoma by suppressing ACSL4-mediated ferroptosis.Respiratory research · 2026Article
- Methods and applications of patient-derived organoid models for immune microenvironment and immunotherapy research in multiple cancer types.Experimental hematology & oncology · 2026Review
- Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026Review
- SLC40A1 (iron transporter): mechanistic regulation, role in disease pathogenesis, and prospects for targeted therapy.Frontiers in cell and developmental biology · 2026Review
- Ferroptosis-induced SUMO2 lactylation counteracts ferroptosis by enhancing ACSL4 degradation in lung adenocarcinoma.Cell discovery · 2025Article
- Advances in novel cell death mechanisms in breast cancer: intersecting perspectives on ferroptosis, cuproptosis, disulfidptosis, and pyroptosis.Molecular cancer · 2025Review
- Transcription factor ZNF266 suppresses cancer progression by modulating CA9-mediated intracellular pH alteration in lung adenocarcinoma.Respiratory research · 2025Article
- Knockdown of TOP2A reverses cisplatin resistance in ovarian cancer by inhibiting EMT via ferroptosis mediated by the TP53/GPX4/SLC7A11 axis.Frontiers in immunology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundFerroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, is associated with chemoresistance in lung adenocarcinoma (LUAD). This study aims to investigate the role of sarcosine in ferroptosis and its underlying mechanisms.
methodsAn RSL3-induced ferroptosis model was used to screen a library of 889 human endogenous metabolites and metabolomic profiling was harnessed to identify metabolites associated with ferroptosis. Cell viability, lipid-reactive oxygen species (ROS), ferrous iron, malondialdehyde (MDA), and mitochondrial integrity were assessed to evaluate sarcosine's effects on ferroptosis. Metabolic fate was studied using
resultsSarcosine emerged as a potent ferroptosis inducer in the metabolic library screening, which was further confirmed via cell viability, lipid-ROS, ferrous iron, and MDA measurements. Metabolic flux analysis showed limited conversion of sarcosine to other metabolites in LUAD cells, while untargeted metabolomic profiling and seahorse assays indicated a metabolic shift from glycolysis to oxidative phosphorylation. Sarcosine enhanced pyruvate dehydrogenase activity to generate more ROS by interacting with PDK4, reducing PDHA1 phosphorylation. As a co-activator of N-methyl-D-aspartate receptor (NMDAR), sarcosine also exerted its pro-ferroptosis effect via regulating ferrous export through the NMDAR/MXD3/SLC40A1 axis. Given the significance of ferroptosis in chemotherapy, we validated that sarcosine enhanced the sensitization of cisplatin by promoting ferroptosis in LUAD cells, PDOs, and xenograft models.
conclusionSarcosine promotes ferroptosis and enhances chemosensitivity, suggesting its potential as a therapeutic agent in treating LUAD.
Indexed as
Identifiers
What OpenQuestion holds
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.