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Zeaxanthin targets TOP2A to regulate autophagy and suppress lung cancer progression via the MAPK/ERK pathway

Jinxi He1, Bo Yu1, Xuyang Song1

  • 1General Thoracic Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, China.

Translational Oncology
|January 7, 2026
PubMed

Insights

Zeaxanthin (Zea) shows potential as a lung cancer (LC) treatment by targeting DNA topoisomerase II A (TOP2A). This natural compound suppresses tumor growth, migration, and proliferation while promoting cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Lung cancer (LC) presents a significant global health burden with limited effective treatments.
  • Zeaxanthin (Zea), a natural carotenoid, possesses antioxidant and anti-tumor properties, but its role in LC is not well understood.

Purpose of the Study:

  • To investigate the anti-cancer mechanisms of Zeaxanthin (Zea) in lung cancer (LC).
  • To identify key molecular targets and pathways affected by Zea in LC progression.

Main Methods:

  • In vitro studies assessing cell viability, proliferation, migration, and apoptosis.
  • Transcriptome analysis, molecular docking, and cellular thermal shift assays to identify and validate Zea-TOP2A interaction.
  • Western blot and immunofluorescence to analyze protein expression and signaling pathways (MAPK/ERK, autophagy).
  • In vivo orthotopic lung cancer models to evaluate tumor growth and molecular changes.

Main Results:

  • Zeaxanthin (Zea) significantly inhibited LC cell viability, proliferation, and migration, while inducing apoptosis.
  • DNA topoisomerase II A (TOP2A) was identified as a direct molecular target of Zea, with Zea enhancing TOP2A protein stability.
  • Zea treatment suppressed TOP2A expression, disrupted MAPK/ERK signaling, and enhanced autophagic activity.
  • In vivo studies confirmed Zea's efficacy in reducing tumor growth and decreasing TOP2A and Ki67 expression.

Conclusions:

  • Zeaxanthin (Zea) demonstrates potent therapeutic potential against lung cancer (LC) by targeting DNA topoisomerase II A (TOP2A).
  • Zea suppresses tumor progression through inhibition of the MAPK/ERK pathway and modulation of autophagy.
  • These findings support Zea as a promising agent for lung cancer treatment.
Keywords:
AutophagyLung cancerMAPK/ERK signaling pathwayTOP2AZeaxanthin

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