TY - JOUR
T1 - H2S-Synthesizing Enzymes Are Putative Determinants in Lung Cancer Management toward Personalized Medicine
AU - Hipólito, Ana
AU - Mendes, Cindy
AU - Martins, Filipa
AU - Lemos, Isabel
AU - Francisco, Inês
AU - Cunha, Fernando
AU - Almodôvar, Teresa
AU - Albuquerque, Cristina
AU - Gonçalves, Luís G
AU - Bonifácio, Vasco D B
AU - Vicente, João B
AU - Serpa, Jacinta
N1 - Funding Information:
The institutions are funded by Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), MOSTMICRO-ITQB (UIDB/04612/2020 and UIDP/04612/2020), and the Associated Laboratory LS4FUTURE (LA/P/0087/2020). The study was partially supported by a Merck KGaA, Darmstadt, Germany, Healthcare Speed Grant in 2021, Ref: 30 attributed to NMS|FCM-UNL. Ana Hipólito was funded by an FCT individual Ph.D. fellowship (SFRH/BD/148441/2019). Cindy Mendes was funded by an FCT individual Ph.D. fellowship (2020.06956.BD). Filipa Martins was funded by an FCT individual Ph.D. fellowship (2020.04780.BD). Isabel Lemos was funded by an FCT individual Ph.D. fellowship (UI/BD/154203/2022). Luis G. Gonçalves was financed by an FCT contract according to DL57/2016, (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:
© 2023 by the authors.
PY - 2024/1
Y1 - 2024/1
N2 - Lung cancer is a lethal disease with no truly efficient therapeutic management despite the progresses, and metabolic profiling can be a way of stratifying patients who may benefit from new therapies. The present study is dedicated to profiling cysteine metabolic pathways in NSCLC cell lines and tumor samples. This was carried out by analyzing hydrogen sulfide (H2S) and ATP levels, examining mRNA and protein expression patterns of cysteine catabolic enzymes and transporters, and conducting metabolomics analysis using nuclear magnetic resonance (NMR) spectroscopy. Selenium-chrysin (SeChry) was tested as a therapeutic alternative with the aim of having an effect on cysteine catabolism and showed promising results. NSCLC cell lines presented different cysteine metabolic patterns, with A549 and H292 presenting a higher reliance on cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) to maintain H2S levels, while the PC-9 cell line presented an adaptive behavior based on the use of mercaptopyruvate sulfurtransferase (MST) and cysteine dioxygenase (CDO1), both contributing to the role of cysteine as a pyruvate source. The analyses of human lung tumor samples corroborated this variability in profiles, meaning that the expression of certain genes may be informative in defining prognosis and new targets. Heterogeneity points out individual profiles, and the identification of new targets among metabolic players is a step forward in cancer management toward personalized medicine.
AB - Lung cancer is a lethal disease with no truly efficient therapeutic management despite the progresses, and metabolic profiling can be a way of stratifying patients who may benefit from new therapies. The present study is dedicated to profiling cysteine metabolic pathways in NSCLC cell lines and tumor samples. This was carried out by analyzing hydrogen sulfide (H2S) and ATP levels, examining mRNA and protein expression patterns of cysteine catabolic enzymes and transporters, and conducting metabolomics analysis using nuclear magnetic resonance (NMR) spectroscopy. Selenium-chrysin (SeChry) was tested as a therapeutic alternative with the aim of having an effect on cysteine catabolism and showed promising results. NSCLC cell lines presented different cysteine metabolic patterns, with A549 and H292 presenting a higher reliance on cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) to maintain H2S levels, while the PC-9 cell line presented an adaptive behavior based on the use of mercaptopyruvate sulfurtransferase (MST) and cysteine dioxygenase (CDO1), both contributing to the role of cysteine as a pyruvate source. The analyses of human lung tumor samples corroborated this variability in profiles, meaning that the expression of certain genes may be informative in defining prognosis and new targets. Heterogeneity points out individual profiles, and the identification of new targets among metabolic players is a step forward in cancer management toward personalized medicine.
KW - 3-mercaptopyruvate sulfurtransferase (MST)
KW - NSCLC metabolism
KW - cystathionine β-synthase (CBS)
KW - cystathionine γ-lyase (CSE)
KW - cysteine dioxygenase (CDO1)
KW - cysteine metabolism
KW - metabolic plasticity
KW - metabolism-based therapies
UR - http://www.scopus.com/inward/record.url?scp=85183131250&partnerID=8YFLogxK
U2 - 10.3390/antiox13010051
DO - 10.3390/antiox13010051
M3 - Article
C2 - 38247476
SN - 2076-3921
VL - 13
JO - Antioxidants
JF - Antioxidants
IS - 1
M1 - 51
ER -