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Regulation of TRAIL-induced apoptosis by ectopic expression of antiapoptotic factors

Bharat B Aggarwal1, Uddalak Bhardwaj, Yasunari Takada

  • 1Cytokine Research Section, Department of Bioimmunotherapy, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Vitamins and Hormones
|April 28, 2004
PubMed

Insights

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows promise as a selective cancer therapy. This review details TRAIL

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was discovered in 1995.
  • TRAIL was heralded as a selective tumor cell killer with high potential.
  • Its molecular activity has been extensively studied.

Purpose of the Study:

  • To review the molecular mechanisms of TRAIL-induced apoptosis.
  • To discuss the cellular factors regulating TRAIL-induced apoptosis.
  • To evaluate TRAIL's selectivity in killing tumor cells versus normal cells.

Main Methods:

  • Interaction of TRAIL with five cell surface receptors (DR4, DR5, DcR1, DcR2, osteoprotegrin).
  • Activation of apoptotic signaling pathways involving FADD, caspases, and mitochondria.
  • Analysis of negative regulatory factors of TRAIL-induced apoptosis.

Main Results:

  • TRAIL triggers apoptosis via caspase-8 and caspase-3 activation.
  • Cleaved Bid leads to mitochondrial cytochrome c release and caspase-9 activation.
  • Numerous cellular factors, including decoy receptors and IAPs, negatively regulate TRAIL-induced apoptosis.

Conclusions:

  • TRAIL-induced apoptosis is a complex process regulated by multiple cellular factors.
  • Understanding these regulatory mechanisms is crucial for optimizing TRAIL-based cancer therapies.
  • The selectivity of TRAIL in killing tumor cells remains a key area of investigation.

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