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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Phenylethyl isothiocyanate induces apoptotic signaling via suppressing phosphatase activity against c-Jun N-terminal

Yi-Rong Chen1, Jin Han, Rajashree Kori

  • 1Department of Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.

The Journal of Biological Chemistry
|August 13, 2002
PubMed

Insights

Phenylethyl isothiocyanate (PEITC) triggers cancer cell death by inhibiting JNK phosphatases, offering a novel therapeutic approach for genotoxic-resistant cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Dietary isothiocyanates are known to induce apoptosis in cancer cells via c-Jun N-terminal kinase (JNK) pathways.
  • Prostate cancer cell lines exhibit varying sensitivities to apoptosis-inducing agents based on their p53 status.

Purpose of the Study:

  • To investigate the mechanism by which phenylethyl isothiocyanate (PEITC) induces apoptosis in prostate cancer cells.
  • To determine if PEITC-induced JNK activation is dependent on upstream kinases or phosphatases.

Main Methods:

  • Treatment of prostate cancer cell lines with PEITC.
  • Analysis of JNK activation, phosphorylation, and dephosphorylation.
  • Assessment of MKK4, MKK7, and M3/6 expression levels.
  • Evaluation of proteasome-dependent degradation pathways.

Main Results:

  • PEITC induced JNK activation and apoptosis in prostate cancer cells regardless of p53 status.
  • PEITC-induced apoptosis occurred through a distinct pathway from DNA-damaging agents, as genotoxic-resistant cells remained sensitive.
  • PEITC did not directly activate JNK or its upstream kinases (MKK4, MKK7).
  • PEITC decreased JNK dephosphorylation rates and down-regulated the JNK-specific phosphatase M3/6 via proteasome degradation.

Conclusions:

  • PEITC activates JNK by suppressing its dephosphorylation, rather than direct activation of JNK or its upstream kinases.
  • PEITC represents a potential therapeutic agent for cancers resistant to conventional genotoxic therapies.
  • JNK phosphatases are identified as potential therapeutic targets for novel cancer treatments.

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