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Soy Isoflavone Genistein Enhances Tamoxifen Sensitivity in Breast Cancer via microRNA and Glucose Metabolism

Jessica Shpigel1, Emilia F Luciano1, Blessing Ukandu1

  • 1Department of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USA.

International Journal of Molecular Sciences
|January 25, 2025
PubMed

Insights

Genistein, a soy isoflavone, combats tamoxifen resistance in estrogen receptor-positive breast cancer by downregulating miR-155. This natural compound also shows potential anti-metastatic and anti-Warburg effect properties.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Estrogen receptor-positive (ER+) breast cancer treatment often involves tamoxifen, an estrogen antagonist.
  • Tamoxifen resistance develops in about 40% of patients, necessitating alternative therapeutic strategies.
  • MicroRNAs, particularly miR-155, have emerged as key regulators in tamoxifen resistance.

Purpose of the Study:

  • To investigate the role of miR-155 in tamoxifen resistance in ER+ breast cancer cells.
  • To evaluate the efficacy of genistein, a soy isoflavone, in overcoming tamoxifen resistance.
  • To explore genistein's effects on miR-155 expression, related molecular targets, and cancer cell behavior.

Main Methods:

  • Comparative analysis of miR-155 expression in tamoxifen-sensitive (TAM-S) and tamoxifen-resistant (TAM-R) MCF-7 breast cancer cells.
  • Overexpression of miR-155 in TAM-S cells to assess its impact on tamoxifen sensitivity.
  • Treatment of cells with genistein to evaluate its effects on miR-155, STAT3, hexokinase 2 (HK2), cell migration, and glucose metabolism.

Main Results:

  • miR-155 was significantly upregulated in TAM-R cells compared to TAM-S cells.
  • Overexpressing miR-155 in TAM-S cells conferred tamoxifen resistance.
  • Genistein downregulated miR-155 and its targets (STAT3, HK2), reduced cell migration, and decreased glucose consumption, suggesting modulation of the Warburg effect.

Conclusions:

  • miR-155 is a critical factor in tamoxifen resistance in ER+ breast cancer.
  • Genistein demonstrates potential as a therapeutic agent to overcome tamoxifen resistance.
  • Genistein may possess anti-metastatic properties and can modulate glucose metabolism in breast cancer cells.
Keywords:
breast cancergenisteinglucose metabolismisoflavonemicroRNAnatural compoundstamoxifen

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