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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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PRODH Regulates Tamoxifen Resistance through Ferroptosis in Breast Cancer Cells

Ping Zhang1, Na Qian1, Haigen Lai1

  • 1The Department of Biochemistry, Medicine School, Yichun University, Yichun 336000, China.

Genes
|October 26, 2024
PubMed
Abstract

Insights

Proline dehydrogenase (PRODH) regulates tamoxifen resistance in breast cancer by controlling ferroptosis. Restoring PRODH function can overcome tamoxifen resistance, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Molecular Biology

Background:

  • Estrogen receptor-positive breast cancer (ER+ BC) is common, with tamoxifen as a primary treatment.
  • Tamoxifen resistance is a significant clinical challenge, often linked to metabolic reprogramming.
  • The role of proline metabolism, specifically proline dehydrogenase (PRODH), in tamoxifen resistance remains unexplored.

Purpose of the Study:

  • To investigate the function and mechanism of PRODH in tamoxifen resistance within breast cancer cells.
  • To determine if PRODH impacts cellular responses to tamoxifen therapy.

Main Methods:

  • Quantitative real-time PCR and Western blot to assess PRODH and GPX4 expression.
  • MTT assays to evaluate breast cell sensitivity to tamoxifen.
  • Trans-well assays for cell migration and invasion analysis.
  • Xenograft tumor assays to study PRODH's in vivo role in tumor growth.
  • Flow cytometry to measure reactive oxygen species levels.

Main Results:

  • PRODH expression was decreased in tamoxifen-resistant cells.
  • Overexpression of PRODH improved tamoxifen response both in vitro and in vivo.
  • PRODH knockdown induced tamoxifen resistance in sensitive cells.
  • Ferroptosis was suppressed in resistant cells; PRODH overexpression restored it.
  • Ferrostatin-1 (Fer-1) reversed PRODH's impact on tamoxifen resistance.

Conclusions:

  • PRODH plays a critical role in regulating tamoxifen resistance in breast cancer.
  • PRODH influences tamoxifen resistance through the modulation of ferroptosis.
  • Targeting PRODH or ferroptosis pathways may offer strategies to overcome tamoxifen resistance.
Keywords:
PRODHferroptosisprolinetamoxifen resistance

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