ArticleCancer discovery2013
Unbiased metabolite profiling indicates that a diminished thymidine pool is the underlying mechanism of colon cancer chemoprevention by alpha-difluoromethylornithine.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Polyamine metabolism in prostate cancer.Current opinion in oncology · 2025Review
- Polyamines mediate cellular energetics and lipid metabolism through mitochondrial respiration to facilitate virus replication.PLoS pathogens · 2024Article
- A polyamine metabolism risk signature for predicting the prognosis and immune therapeutic response of kidney cancer.Translational cancer research · 2023Article
- Polyamines in cancer: integrating organismal metabolism and antitumour immunity.Nature reviews. Cancer · 2022Review
- Difluoromethylornithine (DFMO) and AMXT 1501 inhibit capsule biosynthesis in pneumococci.Scientific reports · 2022Article
- Application of modified Michaelis - Menten equations for determination of enzyme inducing and inhibiting drugs.BMC pharmacology & toxicology · 2021Article
- α-Difluoromethylornithine-Induced Cytostasis is Reversed by Exogenous Polyamines, Not by Thymidine Supplementation.Biomolecules · 2021Article
- Interplay Among Metabolism, Epigenetic Modifications, and Gene Expression in Cancer.Frontiers in cell and developmental biology · 2021Review
- Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy.The Journal of biological chemistry · 2020Article
- Diverse Functions of Polyamines in Virus Infection.Biomolecules · 2020Review
- Basic Hallmarks of Urothelial Cancer Unleashed in Primary Uroepithelium by Interference with the Epigenetic Master Regulator ODC1.Scientific reports · 2020Article
- Patched1 haploinsufficiency severely impacts intermediary metabolism in the skin of Ptch1Scientific reports · 2019Article
- ETHE1 overexpression promotes SIRT1 and PGC1α mediated aerobic glycolysis, oxidative phosphorylation, mitochondrial biogenesis and colorectal cancer.Oncotarget · 2019Article
- Polyamine metabolism and cancer: treatments, challenges and opportunities.Nature reviews. Cancer · 2018Review
- Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease).Scientific reports · 2018Article
- Alpha-Difluoromethylornithine, an Irreversible Inhibitor of Polyamine Biosynthesis, as a Therapeutic Strategy against Hyperproliferative and Infectious Diseases.Medical sciences (Basel, Switzerland) · 2018Review
- Dietary folate levels alter the kinetics and molecular mechanism of prostate cancer recurrence in the CWR22 model.Oncotarget · 2017Article
- Targeting ornithine decarboxylase (ODC) inhibits esophageal squamous cell carcinoma progression.NPJ precision oncology · 2017Article
- Targeting polyamine metabolism for cancer therapy and prevention.The Biochemical journal · 2016Review
- Untargeted metabolite profiling reveals that nitric oxide bioynthesis is an endogenous modulator of carotenoid biosynthesis in Deinococcus radiodurans and is required for extreme ionizing radiation resistance.Archives of biochemistry and biophysics · 2016Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledThe ornithine decarboxylase inhibitor α-difluoromethylornithine (DFMO) is a highly effective chemopreventive agent for colorectal cancer thought to act via polyamine depletion. However, in DFMO-treated patients, mucosal polyamine levels do not directly correlate with colorectal cancer risk. Untargeted metabolite profiling was used to broadly survey DFMO actions on colon cancer cell metabolism. We found that DFMO treatment of Apc(Min) intestinal tumors and human colorectal cancer cells is associated with reduced levels of folate-dependent metabolites, including S-adenosylmethionine (SAM), thymidine pools, and related pathway intermediates. We hypothesized that unrestrained SAM consumption/regeneration constitutes a futile DFMO-triggered cascade that can steal tetrahydrofolate from thymidylate synthase and thereby diminish thymidine pools. In accord with this hypothesis, DFMO treatment altered the folate cofactor balance and thymidine supplementation prevented DFMO-elicited cytostasis without restoring polyamine levels. These findings suggest that thymidine metabolite pool insufficiency is a fundamental mechanism of DFMO cytostatic activity. SIGNIFICANCE: A previously unappreciated metabolic linkage between polyamine and thymidine biosynthesis is revealed, based on the competing requirement of these pathways for a limited pool of tetrahydrofolate cofactor. This study identifies the fi rst shared mechanism for colorectal cancer chemoprevention and chemotherapy, suggesting a common metabolic target for both premalignant and malignant colon cells.
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