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Beta-phenylethyl isothiocyanate mediated apoptosis; contribution of Bax and the mitochondrial death pathway

Peter Rose1, Jeffery S Armstrong, Yee Liu Chua

  • 1Department of Biochemistry, Occupational and Family Medicine, MD3, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore. cofpcr@nus.edu.sg

The International Journal of Biochemistry & Cell Biology
|September 24, 2004
PubMed

Insights

Beta-phenylethyl isothiocyanate (PEITC) triggers apoptosis in HepG2 cells by inducing Bax translocation to mitochondria, leading to cell death. This process involves mitochondrial dysfunction but not the mitochondrial permeability transition (MPT).

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • The precise mechanisms by which chemopreventive agents induce apoptosis remain incompletely understood.
  • Beta-phenylethyl isothiocyanate (PEITC) is a chemopreventive agent whose apoptotic signaling pathways require elucidation.

Purpose of the Study:

  • To investigate the effects of PEITC on mitochondrial function and apoptotic signaling in HepG2 cells and isolated rat hepatocytes.
  • To determine the role of Bax translocation and mitochondrial permeability transition (MPT) in PEITC-induced apoptosis.

Main Methods:

  • Treatment of HepG2 cells and isolated rat hepatocyte mitochondria with PEITC.
  • Assessment of mitochondrial membrane potential (Deltapsim), respiratory chain activity, and cytochrome c release.
  • Analysis of Bax translocation and caspase activation.
  • Evaluation of MPT using pharmacological inhibitors (cyclosporine A, trifluoperazine, Bongkrekic acid).

Main Results:

  • PEITC induced Bax conformational change and its translocation to mitochondria in HepG2 cells.
  • Bax accumulation correlated with loss of Deltapsim, impaired respiration, cytochrome c release, and caspase activation.
  • Caspase inhibition blocked DNA fragmentation and cell death but not upstream events like Bax translocation or cytochrome c release.
  • PEITC did not induce MPT in isolated mitochondria, and MPT inhibitors failed to block PEITC-mediated apoptosis in HepG2 cells.

Conclusions:

  • Mitochondria are a critical target in PEITC-induced apoptosis in HepG2 cells.
  • Apoptosis is mediated via the pore-forming ability of pro-apoptotic Bax, leading to mitochondrial permeabilization.
  • The mechanism involves Bax-dependent pore formation rather than the classical mitochondrial permeability transition (MPT).

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