ArticlePLoS biology2017
Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 60 citations in OpenAlex.
- Resolving challenges in detection and quantification of D-2-hydroxyglutarate and L-2-hydroxyglutarate via LC/MS.Methods (San Diego, Calif.) · 2026Article
- Metabolic pathways fuelling devil facial tumour diseases.The FEBS journal · 2026Article
- Glutamine Deprivation Triggers Tribbles Homolog 3 Dependent G-Quadruplex Resolution to Maintain DNA Repair and Tumor Survival.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Increased vulnerability of colorectal cancer models with high alkylation damage to NTHL1 inactivation.Scientific reports · 2026Article
- Targeting metabolism to combat anticancer and antibacterial drug resistance.Trends in pharmacological sciences · 2026Review
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- ALKBH7 and NLRP3 Co-Expression: A Potential Prognostic and Immunometabolic Marker Set in Breast Cancer Subtypes.International journal of molecular sciences · 2025Article
- Article
- A pancancer analysis reveals the oncogenic role of glutaminase 1 (GLS1) in tumor metabolism and immune evasion: a bioinformatics analysis.Discover oncology · 2025Article
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
- B cell immunometabolism in health and disease.Nature immunology · 2025Review
- Glutamine Metabolism and Prostate Cancer.Cancers · 2024Review
- Unrestricted molecular motions enable mild photothermy for recurrence-resistant FLASH antitumor radiotherapy.Bioactive materials · 2024Article
- Article
- A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability.Molecular systems biology · 2023Article
- DNA Alkylation Damage by Nitrosamines and Relevant DNA Repair Pathways.International journal of molecular sciences · 2023Review
- Article
- Review
- Neddylation inhibition induces glutamine uptake and metabolism by targeting CRL3Nature communications · 2022Article
- CTP sensing and Mec1ATR-Rad53CHK1/CHK2 mediate a two-layered response to inhibition of glutamine metabolism.PLoS genetics · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.
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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.