ArticleProceedings of the National Academy of Sciences of the United States of America2020
Enzyme-mediated depletion of serum l-Met abrogates prostate cancer growth via multiple mechanisms without evidence of systemic toxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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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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
24 citing papers in PubMed, 54 citations in OpenAlex.
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- Methionine restriction and mimetics to ameliorate human aging and disease.Trends in endocrinology and metabolism: TEM · 2026Review
- Integrated production and protein-protein docking analysis of3 Biotech · 2025Article
- Machine-guided dual-objective protein engineering for deimmunization and therapeutic functions.Cell systems · 2025Article
- Methionine Dependency and Restriction in Cancer: Exploring the Pathogenic Function and Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Tumor Integrin-Targeted Glucose Oxidase Enzyme Promotes ROS-Mediated Cell Death that Combines with Interferon Alpha Therapy for Tumor Control.Molecular cancer therapeutics · 2025Article
- Integration of clinical phenoms and metabolomics facilitates precision medicine for lung cancer.Cell biology and toxicology · 2024Article
- Fresh Insights IntoOncology reviews · 2024Review
- Dietary Manipulation of Amino Acids for Cancer Therapy.Nutrients · 2023Review
- Whole-exome sequencing of Indian prostate cancer reveals a novel therapeutic target: POLQ.Journal of cancer research and clinical oncology · 2023Article
- Methionine restriction and cancer treatment: a systems biology study of yeast to investigate the possible key players.Turkish journal of biology = Turk biyoloji dergisi · 2023Article
- Article
- Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer.Nutrients · 2022Article
- Emerging roles of cystathionine β-synthase in various forms of cancer.Redox biology · 2022Review
- Serine, N-acetylaspartate differentiate adolescents with juvenile idiopathic arthritis compared with healthy controls: a metabolomics cross-sectional study.Pediatric rheumatology online journal · 2022Article
- A Computational Model for the PLP-Dependent Enzyme MethionineFrontiers in molecular biosciences · 2022Article
- Circulating metabolites associated with tumor hypoxia and early response to treatment in bevacizumab-refractory glioblastoma after combined bevacizumab and evofosfamide.Frontiers in oncology · 2022Article
- Targeting the methionine addiction of cancer.American journal of cancer research · 2022Review
- The past, present, and future of enzyme-based therapies.Drug discovery today · 2022Review
- Ionizing radiations induce shared epigenomic signatures unraveling adaptive mechanisms of cancerous cell lines with or without methionine dependency.Clinical epigenetics · 2021Article
Corrections and comments
- Commented on byUro-Science.2021
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Extensive studies in prostate cancer and other malignancies have revealed that l-methionine (l-Met) and its metabolites play a critical role in tumorigenesis. Preclinical and clinical studies have demonstrated that systemic restriction of serum l-Met, either via partial dietary restriction or with bacterial l-Met-degrading enzymes exerts potent antitumor effects. However, administration of bacterial l-Met-degrading enzymes has not proven practical for human therapy because of problems with immunogenicity. As the human genome does not encode l-Met-degrading enzymes, we engineered the human cystathionine-γ-lyase (hMGL-4.0) to catalyze the selective degradation of l-Met. At therapeutically relevant dosing, hMGL-4.0 reduces serum l-Met levels to >75% for >72 h and significantly inhibits the growth of multiple prostate cancer allografts/xenografts without weight loss or toxicity. We demonstrate that in vitro, hMGL-4.0 causes tumor cell death, associated with increased reactive oxygen species, S-adenosyl-methionine depletion, global hypomethylation, induction of autophagy, and robust poly(ADP-ribose) polymerase (PARP) cleavage indicative of DNA damage and apoptosis.
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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.