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Updated: Oct 10, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

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Published on: October 5, 2012

Failure of Bcl-2 to block mitochondrial dysfunction during TRAIL-induced apoptosis. Tumor necrosis-related

E J Kim1, A Suliman, A Lam

  • 1Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Greenebaum Cancer Center, Baltimore, MD 21201, USA.

International Journal of Oncology
|December 15, 2000
PubMed

Insights

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells. While Bcl-2 delays TRAIL-induced apoptosis, it does not inhibit it, suggesting TRAIL can target Bcl-2 positive cancer cells.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Immunology

Background:

  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but not normal cells.
  • Bcl-2 is an oncogene that protects cells from apoptosis, but its role in TRAIL-induced apoptosis is unclear.

Purpose of the Study:

  • To investigate whether Bcl-2 regulates apoptosis induced by TRAIL.

Main Methods:

  • Investigated TRAIL-induced apoptosis signaling pathways, including caspase activation, mitochondrial transmembrane potential (Δψm) loss, and cytochrome c release.
  • Utilized Jurkat cells deficient in FADD or caspase-8 to assess TRAIL signaling requirements.
  • Examined the effect of Bcl-2 overexpression on TRAIL-induced apoptosis and compared it to etoposide-induced apoptosis.

Main Results:

  • TRAIL initiates caspase activation, Δψm loss, and cytochrome c release.
  • FADD and caspase-8 are essential for TRAIL signaling.
  • Bcl-2 overexpression delays but does not inhibit TRAIL-induced apoptosis, mitochondrial changes, and cell death.
  • Bcl-2 effectively blocks etoposide-induced apoptosis.
  • Inhibitors like XIAP, CrmA, and p35 block TRAIL-induced apoptosis.

Conclusions:

  • TRAIL-induced apoptosis is regulated by Bcl-2, although not completely inhibited.
  • TRAIL demonstrates potential for selectively targeting Bcl-2 positive cancer cells resistant to conventional chemotherapy.

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