Author(s): 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
Date: 2024
Persistent ID: http://hdl.handle.net/10362/172774
Origin: Repositório Institucional da UNL
Subject(s): Biophysics; Biochemistry; Molecular Biology; Cell Biology; SDG 3 - Good Health and Well-being
Funding Information: The institutions are funded by Fundac\u00B8 \u00E3o para a Ci\u00EAncia e a Tecnologia/Minist\u00E9rio da Ci\u00EAncia, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNO-VA4Health [grant numbers UIDB/04462/2020 and UIDP/04462/2020], to MOSTMICRO-ITQB [grant numbers UIDB/04612/2020 and UIDP/04612/2020] and the Associated Laboratory LS4FUTURE [grant number LA/P/0087/2020]. During the course of PhD, Cindy Mendes was funded by Liga Portuguesa Contra o Cancro -Nucleo regional Sul (LPCC-NRS) and by an FCT individual Ph.D. fellowship [grant number 2020.06956.BD]. Isabel Lemos was funded by an FCT individual Ph.D. fellowship [grant number UI/BD/154203/2022]. Ana Hip\u00F3lito was funded by a FCT individual Ph.D. fellowship [grant number SFRH/BD/148441/2019]. Filipa Martins was funded by a FCT individual Ph.D. fellowship (2020.04780.BD). Luis G. Gonc\u00B8 alves was financed by a FCT contract according to DL57/2016, [grant number SFRH/BPD/111100/2015]. This work benefited from access to CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT, project AAC 01/SAICT/2016. Publisher Copyright: © 2024 The Author(s).
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.
