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

Ana Hipólito1,2, Cindy Mendes1,2, Filipa Martins1,2

  • 1iNOVA4Health, NOVA Medical School, 1150-069 Lisbon, Portugal.

Antioxidants (Basel, Switzerland)
|January 22, 2024
PubMed

Insights

Lung cancer patients show varied cysteine metabolism, impacting treatment strategies. Understanding these metabolic profiles, including hydrogen sulfide (H2S) production, aids in developing personalized therapies for non-small cell lung cancer (NSCLC).

Area of Science:

  • Oncology
  • Biochemistry
  • Metabolomics

Background:

  • Lung cancer remains a significant health challenge with limited therapeutic options.
  • Metabolic profiling offers a potential avenue for patient stratification and identifying novel treatment targets.
  • Cysteine metabolism plays a crucial role in cellular processes and cancer progression.

Purpose of the Study:

  • To profile cysteine metabolic pathways in non-small cell lung cancer (NSCLC) cell lines and tumor samples.
  • To investigate the role of specific enzymes and transporters in cysteine catabolism and hydrogen sulfide (H2S) production.
  • To evaluate selenium-chrysin (SeChry) as a potential therapeutic agent targeting cysteine metabolism.

Main Methods:

  • Analysis of hydrogen sulfide (H2S) and ATP levels.
  • Examination of mRNA and protein expression of cysteine catabolic enzymes and transporters.
  • Metabolomics analysis using nuclear magnetic resonance (NMR) spectroscopy.
  • Assessment of selenium-chrysin (SeChry) efficacy.

Main Results:

  • NSCLC cell lines exhibit distinct cysteine metabolic patterns.
  • A549 and H292 cell lines rely on cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) for H2S maintenance.
  • PC-9 cell line utilizes mercaptopyruvate sulfurtransferase (MST) and cysteine dioxygenase (CDO1) for cysteine-to-pyruvate conversion.
  • Human lung tumor samples confirm metabolic heterogeneity.
  • Selenium-chrysin (SeChry) demonstrated promising therapeutic effects.

Conclusions:

  • Cysteine metabolic heterogeneity is a key feature of NSCLC.
  • Specific metabolic enzyme expression can inform prognosis and identify therapeutic targets.
  • Targeting cysteine metabolism represents a promising strategy for personalized lung cancer medicine.
Keywords:
3-mercaptopyruvate sulfurtransferase (MST)NSCLC metabolismcystathionine β-synthase (CBS)cystathionine γ-lyase (CSE)cysteine dioxygenase (CDO1)cysteine metabolismmetabolic plasticitymetabolism-based therapies

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