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Despite progress in therapeutic interventions, encompassing surgical procedures, radiation, chemotherapy, targeted therapies and immunotherapy, the overall prognosis remains unfavorable. Imbalances in redox equilibrium and disrupted redox signaling, common traits in tumors, play crucial roles in malignant progression and treatment resistance. Cancer cells, often characterized by persistent high levels of reactive oxygen species (ROS) resulting from genetic, metabolic, and microenvironmental alterations, counterbalance this by enhancing their antioxidant capacity. Cysteine availability emerges as a critical factor in chemoresistance, shaping the survival dynamics of non-small cell lung cancer (NSCLC) cells. Selenium-chrysin (SeChry) was disclosed as a modulator of cysteine intracellular availability. This study comprehensively characterizes the metabolism of SeChry and investigates its cytotoxic effects in NSCLC. SeChry treatment induces notable metabolic shifts, particularly in selenocompound metabolism, impacting crucial pathways such as glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. Additionally, SeChry affects the levels of key metabolites such as acetate, lactate, glucose, and amino acids, contributing to disruptions in redox homeostasis and cellular biosynthesis. The combination of SeChry with other treatments, such as glycolysis inhibition and chemotherapy, results in greater efficacy. Furthermore, by exploiting NSCLC's capacity to consume lactate, the use of lactic acid-conjugated dendrimer nanoparticles for SeChry delivery is investigated, showing specificity to cancer cells expressing monocarboxylate transporters.<\/jats:p>","DOI":"10.1042\/bsr20240752","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T14:20:48Z","timestamp":1720707648000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cells"],"prefix":"10.1042","volume":"44","author":[{"given":"Cindy","family":"Mendes","sequence":"first","affiliation":[{"name":"1iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"},{"name":"2Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto 1099-023, Lisboa, Portugal"}]},{"given":"Isabel","family":"Lemos","sequence":"additional","affiliation":[{"name":"1iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"},{"name":"2Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto 1099-023, Lisboa, Portugal"}]},{"given":"Ana","family":"Hip\u00f3lito","sequence":"additional","affiliation":[{"name":"2Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto 1099-023, Lisboa, Portugal"}]},{"given":"Bruna","family":"Abreu","sequence":"additional","affiliation":[{"name":"1iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"},{"name":"2Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto 1099-023, Lisboa, Portugal"}]},{"given":"Catarina","family":"Freitas-Dias","sequence":"additional","affiliation":[{"name":"1iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"},{"name":"2Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto 1099-023, Lisboa, Portugal"}]},{"given":"Filipa","family":"Martins","sequence":"additional","affiliation":[{"name":"1iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"},{"name":"2Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto 1099-023, Lisboa, Portugal"}]},{"given":"Rita\u00a0F.","family":"Pires","sequence":"additional","affiliation":[{"name":"3IBB - Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. 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