Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cells

• Published in: Bioscience reports 2024-07, Vol.44 (7)
• Main Authors: Mendes, Cindy, Lemos, Isabel, Hipólito, Ana, Abreu, Bruna, Freitas-Dias, Catarina, Martins, Filipa, Pires, Rita F, Barros, Hélio, Bonifácio, Vasco D B, Gonçalves, Luís G, Serpa, Jacinta
• Format: Article
• Language: English
• Subjects: A549 Cells; Acetic acid; Amino acids; Availability; Biosynthesis; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell death; Cell Line, Tumor; Cell survival; Chemoresistance; Chemotherapy; Cysteine; Cytotoxicity; Drug resistance; Flavonoids; Flow cytometry; Gluconeogenesis; Glycolysis; Homeostasis; Humans; Immunotherapy; Kinases; Lactic acid; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical prognosis; Metabolism; Metabolites; Metabolomics; Metastasis; Mortality; Mutation; Nanoparticles; NMR; Non-small cell lung carcinoma; Nuclear magnetic resonance; Ovarian cancer; Oxidative stress; Pharmacology & Toxicology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Selenium; Selenium - metabolism; Selenium - pharmacology; Small cell lung carcinoma; Spectrum analysis; Therapeutic applications; Treatment resistance; Tricarboxylic acid cycle; Tumors
• ISSN: 0144-8463; 1573-4935; 1573-4935
• DOI: 10.1042/BSR20240752

Lung cancer ranks as the predominant cause of cancer-related mortalities on a global scale. 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.