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Diallyl trisulfide-induced prostate cancer cell death is associated with Akt/PKB dephosphorylation mediated by

Andzelika Borkowska1, Alicja Sielicka-Dudzin, Anna Herman-Antosiewicz

  • 1Department of Bioenergetics and Physiology of Exercise, Medical University of Gdańsk, Dębinki 1, 80-211, Gdańsk, Poland.

European Journal of Nutrition
|October 25, 2011
PubMed
Abstract

Insights

Diallyl trisulfide (DATS) triggers prostate cancer cell death by phosphorylating p66Shc, a key adaptor protein. Inhibiting this phosphorylation protects cells and alters Akt signaling, revealing a new pathway for DATS action.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • p66Shc adaptor protein mediates cell signaling pathways involved in apoptosis and proliferation.
  • Diallyl trisulfide (DATS) has been shown to induce prostate cancer cell death via reactive oxygen species (ROS) generation.

Purpose of the Study:

  • To investigate the role of p66Shc protein and its serine 36 phosphorylation in DATS-induced reduction of prostate cancer cell viability (PC-3).

Main Methods:

  • Utilized PC-3 prostate cancer cells and stable cell lines expressing p66ShcS36A variant or empty vector.
  • Assessed cell viability, ROS concentration, and levels of phosphorylated p66Shc (P-p66Shc) and phosphorylated Akt (P-Akt), alongside DNA damage.

Main Results:

  • DATS treatment increased p66Shc phosphorylation at serine 36, which was inhibited by SP600125 (JNK inhibitor).
  • Cells expressing p66ShcS36A variant exhibited resistance to DATS-induced cell death and abolished DATS-induced ROS formation.
  • DATS-induced Akt inactivation was prevented by SP600125 and significantly reduced in cells expressing p66ShcS36A, indicating p66Shc's role in Akt dephosphorylation.

Conclusions:

  • p66Shc is essential for DATS-induced Akt inactivation through hypophosphorylation.
  • A novel signaling pathway involving p66Shc in DATS-induced prostate cancer cell death is uncovered.

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