TRAIL Induced Apoptosis - A Prostate Cancer Therapy

Abstract

Five of six prostate cancer cell lines undergo apoptosis when incubated with% TRAIL. Cell viability curves of six prostate cancer cell lines using varying amounts of TRAIL protein were completed. Prostate cancer cell lines Alva 31, PC-3 and DU 145 are highly sensitive to apoptosis induced by TRAIL, while the cell lines TSU-prl and JCA-l are moderately sensitive, and the LNCaP cell line is resistant. Protein synthesis inhibitor cycloheximide and AKT inhibitors wortmannin and LY294OO2 enhance the apoptotic effect of TRAIL. The potential mechanism for resistance to Trail-induced apoptosis in prostate cancer cells was examined. No correlation was found between the sensitivity of cells to TRAIL and the expression of TRAIL receptors DR4 and DR5, decoy receptors for TRAIL DcRl and DcR2, or apoptosis inhibitory protein cFLip. Trail-induced apoptotic signaling in resistant cell line LNCaP is blocked at the level of Bid cleavage, and cytochrome C is not released from mitochondria. Cytochrome C is released from mitochondria when TRAIL is used in combination with wortmanin and to a lesser extent cycloheximide.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2000
Accession Number
ADA387624

Entities

People

  • David M. Rodman
  • Xiaojun Lu

Organizations

  • University of Colorado Boulder

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Culture Media
  • Cytochromes
  • Enzyme Inhibitors
  • Fungi
  • Inhibitors
  • Materials
  • Mitochondria
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Resistance

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Oncology (Cancer Research).