Metabolites, 2023-06, Vol.13 (7), p.774
2023
Details
- Autor(en) / Beteiligte
- Titel
- Differential Inhibition of Anaplerotic Pyruvate Carboxylation and Glutaminolysis-Fueled Anabolism Underlies Distinct Toxicity of Selenium Agents in Human Lung Cancer
- Ist Teil von
- Metabolites, 2023-06, Vol.13 (7), p.774
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2023
- Link zum Volltext
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- Past chemopreventive human trials on dietary selenium supplements produced controversial outcomes. They largely employed selenomethionine (SeM)-based diets. SeM was less toxic than selenite or methylseleninic acid (MSeA) to lung cancer cells. We thus investigated the toxic action of these Se agents in two non-small cell lung cancer (NSCLC) cell lines and ex vivo organotypic cultures (OTC) of NSCLC patient lung tissues. Stable isotope-resolved metabolomics (SIRM) using C -glucose and C N -glutamine tracers with gene knockdowns were employed to examine metabolic dysregulations associated with cell type- and treatment-dependent phenotypic changes. Inhibition of key anaplerotic processes, pyruvate carboxylation (PyC) and glutaminolysis were elicited by exposure to MSeA and selenite but not by SeM. They were accompanied by distinct anabolic dysregulation and reflected cell type-dependent changes in proliferation/death/cell cycle arrest. NSCLC OTC showed similar responses of PyC and/or glutaminolysis to the three agents, which correlated with tissue damages. Altogether, we found differential perturbations in anaplerosis-fueled anabolic pathways to underlie the distinct anti-cancer actions of the three Se agents, which could also explain the failure of SeM-based chemoprevention trials.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2218-1989eISSN: 2218-1989DOI: 10.3390/metabo13070774Titel-ID: cdi_doaj_primary_oai_doaj_org_article_d138aeef22d54272a4f32cf81e8a1281
- Format
- –
- Schlagworte
- Apoptosis, Biosynthesis, Cancer, Cancer therapies, Carboxylation, Care and treatment, Cell cycle, Cell death, Cell growth, Clinical trials, Dietary supplements, Disease prevention, Glucose, Glutamine, glutaminolysis, Isotopes, Lipids, Lung cancer, Lung cancer, Non-small cell, Medical prognosis, Metabolism, Metabolites, Metabolomics, Metastasis, methylseleninic acid, NMR, non-small cell lung cancer, Non-small cell lung carcinoma, Nuclear magnetic resonance, Prevention, Prostate cancer, pyruvate carboxylation, Pyruvic acid, Scientific equipment and supplies industry, Selenite, Selenium, Selenomethionine, Small cell lung carcinoma, Toxicity, Tumor cell lines, Tumors