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Updated: Jun 6, 2025

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
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An Orthotopic Murine Model of Human Prostate Cancer Metastasis

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Effect of Soy Isoflavone on Prostate Cancer Cell Apoptosis Through Inhibition of STAT3, ERK, and AKT

Yoon-Jin Lee1, Changyeol Lee1, Dongsic Choi1

  • 1Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31511, Republic of Korea.

Current Issues in Molecular Biology
|November 26, 2024
PubMed

Insights

Genistein, a soy isoflavone, effectively inhibits prostate cancer DU145 cell growth and induces apoptosis. It achieves this by disrupting mitochondrial function and downregulating key cancer-promoting pathways like STAT3, AKT, and ERK.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Genistein, a soy isoflavone, possesses known antioxidant, anti-inflammatory, and anticancer properties.
  • Prostate cancer remains a significant health concern, necessitating the exploration of novel therapeutic agents.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying genistein's anticancer effects in human prostate cancer DU145 cells.
  • To investigate genistein's impact on cell viability, apoptosis, mitochondrial function, and key signaling pathways.

Main Methods:

  • Flow cytometry was used to assess cell viability, apoptosis (Annexin V staining), and cell cycle distribution (sub-G0/G1 and G2/M phases).
  • Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) production and mitochondrial membrane potential.
  • Western blotting and activity assays were employed to analyze the expression and activity of proteins including p53, caspases, PARP, STAT3, AKT, ERK, p38, and VEGF.

Main Results:

  • Genistein significantly reduced DU145 cell viability and induced apoptosis, evidenced by increased Annexin V-positive cells and a higher sub-G0/G1 cell population.
  • Genistein treatment led to increased ROS production, mitochondrial depolarization, and inhibited ATP synthesis, indicating mitochondrial dysfunction.
  • Genistein upregulated p53, increased caspase-3/7 activity, and promoted the cleavage of Bax, procaspase-3, and PARP. It also inhibited STAT3, AKT, ERK, p38 activation, and decreased VEGF expression.
  • Genistein demonstrated minimal toxicity to normal prostate epithelial cells (HPrEC) at therapeutic concentrations.

Conclusions:

  • Genistein effectively inhibits prostate cancer DU145 cell proliferation and induces apoptosis through multiple molecular mechanisms.
  • The observed anticancer effects are mediated by inducing mitochondrial dysfunction, activating the p53-caspase pathway, and inhibiting pro-survival signaling pathways (STAT3, AKT, ERK, p38).
  • Genistein presents a promising therapeutic candidate for prostate cancer, warranting further investigation for clinical application.
Keywords:
STAT3apoptosisgenisteinprostate cancerreactive oxygen species

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