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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

Notch activation by phenethyl isothiocyanate attenuates its inhibitory effect on prostate cancer cell migration

Su-Hyeong Kim1, Anuradha Sehrawat, Kozue Sakao

  • 1Department of Pharmacology and Chemical Biology, and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

Plos One
|November 1, 2011
PubMed

Insights

Phenethyl isothiocyanate (PEITC), found in cruciferous vegetables, activates Notch signaling in prostate cells, influencing cancer cell apoptosis and migration. Combining PEITC with Notch inhibitors may enhance its anti-metastatic effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Chemoprevention

Background:

  • Phenethyl isothiocyanate (PEITC) is a cruciferous vegetable compound with demonstrated efficacy against prostate cancer.
  • PEITC's chemopreventive effects are linked to its inhibition of oncogenic pathways like NF-κB, Akt, and androgen receptor.

Purpose of the Study:

  • To investigate the effect of PEITC on Notch signaling in human prostate cancer and normal prostate cells.
  • To elucidate the role of Notch signaling in PEITC-mediated apoptosis and migration inhibition in prostate cancer.

Main Methods:

  • Exposure of prostate cell lines (LNCaP, PC-3, DU145, PrEC) to PEITC.
  • Analysis of Notch1/Notch2 cleavage, transcriptional activity, ligand/receptor expression, and γ-secretase components.
  • Assessment of apoptosis and cell migration using RNA interference and pharmacological inhibitors.
  • In vivo studies using mouse xenografts and TRAMP mice.

Main Results:

  • PEITC treatment activated Notch1 and Notch2 signaling in all tested prostate cell lines.
  • Notch2 played a significant role in mediating PEITC-induced apoptosis and migration inhibition.
  • PEITC-induced anti-metastatic effects were augmented by Notch inhibition.
  • Increased nuclear Notch2 was observed in vivo in PEITC-treated models.

Conclusions:

  • PEITC activates Notch signaling in prostate cells, impacting key cancer processes.
  • Targeting Notch signaling in combination with PEITC may represent a novel strategy for enhancing prostate cancer treatment, particularly for metastasis.
  • The findings suggest a potential therapeutic approach combining PEITC with Notch inhibitors for improved anti-metastatic outcomes.

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