ArticleInternational journal of cancer2009
Methionine depletion with recombinant methioninase: in vitro and in vivo efficacy against neuroblastoma and its synergism with chemotherapeutic drugs.
Article in International journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 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
- Epigenetic crosstalk in neuroblastoma development and progression.Frontiers in cell and developmental biology · 2026Review
- Pharmacokinetic/pharmacodynamic model of a methionine starvation based anti-cancer drug.Medical & biological engineering & computing · 2023Article
- Human arginase I: a potential broad-spectrum anti-cancer agent.3 Biotech · 2023Review
- Loss of MAT2A compromises methionine metabolism and represents a vulnerability in H3K27M mutant glioma by modulating the epigenome.Nature cancer · 2022Article
- Predictive markers for efficiency of the amino-acid deprivation therapies in cancer.Frontiers in medicine · 2022Article
- Enzyme-mediated depletion of serum l-Met abrogates prostate cancer growth via multiple mechanisms without evidence of systemic toxicity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Amino Acid Degrading Enzymes and Autophagy in Cancer Therapy.Frontiers in pharmacology · 2020Review
- METase/lncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy.Journal of cancer research and clinical oncology · 2019Article
- Methylseleninic Acid Induces Lipid Peroxidation and Radiation Sensitivity in Head and Neck Cancer Cells.International journal of molecular sciences · 2019Article
- Exploiting Signaling Pathways and Immune Targets Beyond the Standard of Care for Ewing Sarcoma.Frontiers in oncology · 2019Review
- The mechanism study of lentiviral vector carrying methioninase enhances the sensitivity of drug-resistant gastric cancer cells to Cisplatin.British journal of cancer · 2018Article
- Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions.Cancer discovery · 2016Review
- Purification, Characterization of L-Methioninase from Candida tropicalis, and Its Application as an Anticancer.Biotechnology research international · 2015Article
- Dual-porosity hollow nanoparticles for the immunoprotection and delivery of nonhuman enzymes.Nano letters · 2014Article
- Evaluation of the retinoids with cisplatin and vincristine in xenograft models of neuroblastoma.Journal of pediatric hematology/oncology · 2014Article
- L-methionase: a therapeutic enzyme to treat malignancies.BioMed research international · 2014Review
- GFP reporter screens for the engineering of amino acid degrading enzymes from libraries expressed in bacteria.Methods in molecular biology (Clifton, N.J.) · 2013Article
- A synergetic screening approach with companion effector for combination therapy: application to retinoblastoma.PloS one · 2013Article
- De novo engineering of a human cystathionine-γ-lyase for systemic (L)-Methionine depletion cancer therapy.ACS chemical biology · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Methionine starvation can modulate gene methylation, cell cycle transition and pathways related to survival following DNA damage. Methionine depletion by recombinant methioninase (rMETase) may have in vitro and in vivo efficacy against neuroblastoma (NB), especially when combined with chemotherapeutic drugs. rMETase from Pseudomonas putida was produced in Escherichia coli and purified by ion-exchange chromatography. rMETase alone inhibited the proliferation of 15/15 NB cell lines in vitro. Among these 15 cell lines, only 66N demonstrated rMETase-induced apoptosis. rMETase alone suppressed LAN-1 and NMB-7 xenografts (p < 0.01) and no toxicities were noted other than reversible weight loss. In vitro efficacy experiments combining rMETase and chemotherapeutic agents were carried out using SK-N-LD and SK-N-BE (1)N established at diagnosis, as well as LAN-1, SK-N-BE (2)C and NMB-7 established at relapse. Microtubule depolymerization agents including vincristine, vinorelbine, vinblatine and mebendazole showed synergism when tested in combination with rMETase in all 5 cell lines. Among DNA damaging agents, synergy with rMETase was observed only in cell lines established at diagnosis and not at relapse. Cell cycle analysis showed that rMETase arrested G2 phase and not M phase. In vivo efficacy experiments using LAN-1 and NMB-7 xenografts showed that rMETase rendered vincristine more effective than vincristine alone in tumor growth suppression (p < 0.001). In conclusion, methionine depletion inhibited NB proliferation and arrested tumor cells at G2 phase. rMETase synergized with microtubule depolymerization agents. Moreover, synergism between rMETase and DNA damaging agents was dependent on whether cell lines were established at diagnosis or at relapse.
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