ArticleThe Journal of biological chemistry2020
Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 73 citations in OpenAlex.
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- Spermine Oxidase Serves as a Key Functional Node in Microbial Dysbiosis-Induced Breast Carcinogenesis.Cancer research · 2026Article
- Opposing Roles for ATP13A2 and ATP13A3 in Breast Cancer Subtype-Specific Polyamine Homeostasis.Biomolecules · 2026Article
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- ODC-Driven Polyamines Synthesis Sustains the Self-Renewal of Glioblastoma Stem Cells and Drives Tumor Aggressiveness.Cancer science · 2025Article
- KDM4C inhibition blocks tumor growth in basal breast cancer by promoting cathepsin L-mediated histone H3 cleavage.Nature genetics · 2025Article
- The Effect of Microbiome-Derived Metabolites in Inflammation-Related Cancer Prevention and Treatment.Biomolecules · 2025Review
- Arginine: at the crossroads of nitrogen metabolism.The EMBO journal · 2025Review
- Subtype-specific transcription factors affect polyamine metabolism and the tumor microenvironment in breast cancer.Cancer innovation · 2025Article
- Metabolic plasticity drives specific mechanisms of chemotherapy and targeted therapy resistance in metastatic colorectal cancer.Exploration of targeted anti-tumor therapy · 2025Review
- Metabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model study.Frontiers in molecular biosciences · 2024Article
- Disclosing a metabolic signature of cisplatin resistance in MDA-MB-231 triple-negative breast cancer cells by NMR metabolomics.Cancer cell international · 2023Article
- Loss of Anti-Tumor Efficacy by Polyamine Blocking Therapy in GCN2 Null Mice.Biomedicines · 2023Article
- A back-door insight into the modulation of Src kinase activity by the polyamine spermidine.eLife · 2023Article
- A newAmino acids · 2023Article
- Epigenetic-Metabolic Interplay in the DNA Damage Response and Therapeutic Resistance of Breast Cancer.Cancer research · 2023Article
- JAK-STAT Signaling in Inflammatory Breast Cancer Enables Chemotherapy-Resistant Cell States.Cancer research · 2023Article
- Pharmacometabolomics reveals urinary diacetylspermine as a biomarker of doxorubicin effectiveness in triple negative breast cancer.NPJ precision oncology · 2022Article
- Understanding the Polyamine and mTOR Pathway Interaction in Breast Cancer Cell Growth.Medical sciences (Basel, Switzerland) · 2022Article
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6 authors at 2 institutions in 1 country.
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Abstract
Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.
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