TRAIL-Induced Apoptosis - A Prostate Cancer Therapy

Abstract

TRAIL induces apoptosis in five of six prostate cancer cell lines. The cell line LNCaP is resistant to TRAIL treatment. Highly constitutive expression of AKT was found in LNCaP cells, and suppression of AKT activity by the PI-3 kinase inhibitors wortmanin and Ly 294002 renders LNCaP cells sensitive to TRAIL. Infection of LNCaP cells with a constitutively active AKT reverses the wortmanin effect. Thus, elevated AKT protects LNCaP cells from TRAIL-induced apoptosis. Bcl-2 dimerization varies in six different prostate cell lines. Overexpression of bcl-2 in LNCaP cells inhibits cytochrome c release from mitochondria when TRAIL is used in combination with wortmanin, suggesting that the mitochondria mediated apoptosis pathway is crucial. The role of mitochondrial superoxide production in TRAIL-induced apoptosis is currently being studied in smooth muscle cells deficient in each superoxide dismutase.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2001
Accession Number
ADA396623

Entities

People

  • David Rodman
  • Xiaojun Lu

Organizations

  • University of Colorado Boulder

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biomedical Research
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Enzyme Inhibitors
  • Health Services
  • Infection
  • Intracellular Membranes
  • Muscle Cells
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Proteins

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biochemistry
  • Oncology (Cancer Research).