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Published on: September 13, 2018

Lathyrol Targets G6PD to Disrupt Redox Homeostasis in Non-Small Cell Lung Cancer

Zhaoxuan Li1,2, Linlin Zhang2, Xueyan Zhen1,3

  • 1Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

ACS Omega
|August 8, 2026
PubMed

Insights

Lathyrol, a natural compound, targets glucose-6-phosphate dehydrogenase (G6PD) in lung cancer cells. This inhibition disrupts cellular metabolism and redox balance, offering new therapeutic insights.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Lathyrol, a natural compound from Euphorbiaceae plants, shows antitumor potential.
  • Its specific molecular targets and mechanisms in non-small cell lung cancer (NSCLC) are not fully understood.

Purpose of the Study:

  • To systematically identify lathyrol-binding proteins in NSCLC cells.
  • To elucidate the molecular mechanisms underlying lathyrol's antitumor activity.

Main Methods:

  • Thermal proteome profiling (TPP) to identify lathyrol-binding proteins.
  • Cellular thermal shift assay (CETSA) and peptide-centric local stability assay (PELSA) to validate target engagement.
  • Enzymatic assays and quantitative proteomics to assess functional consequences.

Main Results:

  • TPP identified glucose-6-phosphate dehydrogenase (G6PD) as a primary lathyrol-binding protein.
  • CETSA and PELSA confirmed direct interaction and conformational changes in G6PD.
  • Lathyrol treatment reduced G6PD activity, decreased intracellular NADPH, and altered glucose metabolism and redox pathways.

Conclusions:

  • G6PD is a functional target of lathyrol in NSCLC.
  • Lathyrol inhibits G6PD, disrupting cellular redox balance and metabolic homeostasis.
  • These findings provide a mechanistic basis for lathyrol's antitumor effects and suggest G6PD as a therapeutic target.

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