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Updated: Jun 15, 2025

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FXN targeting induces cell death in ovarian cancer stem-like cells through PRDX3-Mediated oxidative stress

Shanshan Xu1, Yuwan Liu2, Shizhou Yang1

  • 1Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China.

Iscience
|August 26, 2024
PubMed

Insights

Elevated FXN in ovarian cancer stem cells (OCSCs) promotes ferroptosis resistance by suppressing reactive oxygen species (ROS). Targeting FXN may offer a new therapeutic strategy for ovarian cancer (OC).

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Ovarian cancer stem cells (OCSCs) are crucial in ovarian cancer (OC) progression, chemoresistance, and poor prognosis.
  • Ferroptosis is a promising therapeutic strategy against OCSCs, but its regulation by OCSCs is not fully understood.

Purpose of the Study:

  • To investigate the role of Frataxin (FXN) in ferroptosis regulation within ovarian cancer stem-like cells (OCSLCs).
  • To explore FXN as a potential therapeutic target for ovarian cancer.

Main Methods:

  • Enrichment of OCSLCs using mammosphere culture.
  • Assessment of ferroptosis susceptibility, stemness markers (Nanog), sphere-forming ability, reactive oxygen species (ROS) levels, and cell viability.
  • FXN knockdown and overexpression studies.
  • Evaluation of OCSLC xenograft tumor growth and peroxiredoxin 3 (PRDX3) levels.

Main Results:

  • OCSLCs exhibit higher ferroptosis susceptibility linked to elevated FXN levels.
  • FXN knockdown reduces stemness, sphere formation, and OCSLC viability while increasing ROS.
  • FXN overexpression confers ferroptosis resistance.
  • FXN knockdown inhibits tumor growth and affects PRDX3, a key antioxidant protein.

Conclusions:

  • Elevated FXN in OCSLCs suppresses ROS accumulation, conferring resistance to ferroptosis.
  • FXN plays a critical role in regulating OCSC stemness and ferroptosis resistance.
  • FXN represents a potential therapeutic target for overcoming chemoresistance in ovarian cancer.
Keywords:
CancerCell biologyMolecular biology

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