H2S-Synthesizing Enzymes Are Putative Determinants in Lung Cancer Management toward Personalized Medicine

Ana Hipólito, Cindy Mendes, Filipa Martins, Isabel Lemos, Inês Francisco, Fernando Cunha, Teresa Almodôvar, Cristina Albuquerque, Luís G Gonçalves, Vasco D B Bonifácio, João B Vicente, Jacinta Serpa

Research output: Contribution to journalArticlepeer-review

6 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number51
JournalAntioxidants
Volume13
Issue number1
Early online date28 Dec 2023
DOIs
Publication statusPublished - Jan 2024

Keywords

  • 3-mercaptopyruvate sulfurtransferase (MST)
  • NSCLC metabolism
  • cystathionine β-synthase (CBS)
  • cystathionine γ-lyase (CSE)
  • cysteine dioxygenase (CDO1)
  • cysteine metabolism
  • metabolic plasticity
  • metabolism-based therapies

Fingerprint

Dive into the research topics of 'H2S-Synthesizing Enzymes Are Putative Determinants in Lung Cancer Management toward Personalized Medicine'. Together they form a unique fingerprint.

Cite this