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Updated: Jul 2, 2026

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

Glycogen synthase kinase 3beta regulates cell death induced by synthetic triterpenoids

Roberta Venè1, Patrizia Larghero, Giuseppe Arena

  • 1Molecular Oncology and Angiogenesis Laboratory, Istituto Nazionale per la Ricerca sul Cancro (IST), Genova, Italy.

Cancer Research
|September 2, 2008
PubMed

Insights

The synthetic triterpenoid CDDO-Me induces programmed cell death in prostate cancer cells. This compound activates caspase-independent pathways and modulates glycogen synthase kinase 3beta (GSK3beta) activity, suggesting a novel therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Programmed cell death induction is a key strategy for controlling prostate cancer.
  • Synthetic oleanane triterpenoids, like CDDO-Me, show potential as chemopreventive agents.

Purpose of the Study:

  • To investigate the mechanism of cell death induced by CDDO-Me in human prostate cancer cells.
  • To explore the role of glycogen synthase kinase 3beta (GSK3beta) in CDDO-Me-mediated cytotoxicity.

Main Methods:

  • Treatment of androgen-responsive and unresponsive prostate cancer cell lines (PC3, DU145) with CDDO-Me.
  • Assays for caspase activation, poly(ADP-ribose) polymerase cleavage, DNA fragmentation, and cell viability.
  • Inhibition of caspases and GSK3beta (using inhibitors or gene silencing) to assess their role in CDDO-Me cytotoxicity.

Main Results:

  • CDDO-Me induced apoptosis markers (caspase activation, DNA fragmentation) and reduced cell viability in prostate cancer cells.
  • Caspase inhibition did not fully rescue cell death, indicating caspase-independent mechanisms.
  • CDDO-Me induced inactivating phosphorylation of GSK3beta, and GSK3 inhibition sensitized cells to CDDO-Me.

Conclusions:

  • CDDO-Me effectively induces cell death in prostate cancer cells through both caspase-dependent and -independent pathways.
  • Modulation of GSK3beta activity is implicated in the cytotoxic effects of CDDO-Me.
  • CDDO-Me represents a promising therapeutic agent for prostate cancer, potentially by targeting GSK3beta.

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