TRAIL: A Novel Therapeutic Agent for Prostate Cancer

Abstract

This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo. We found that most of prostate cancer cells such as androgen-independent PC-3 and DU145 cells are sensitive to TRAIL treatment while normal prostate epithelial cells are resistant. This result indicates that TRAIL may be appropriate agent for treatment of late-stage prostate cancer with no cytotoxicity to normal prostate cells. Further investigation on the molecular mechanism of TRAIL resistance revealed that the elevated eNOS activity by Akt phosphorylation may partially contribute to Akt-mediated TRAIL resistance in LNCaP cells. We also found that chemotherapeutic agents such as etoposide (DNA topoisomearse II inhibitor) and VELCADE (proteasome inhibitor) sensitized PC cells to TRAIL-mediated apoptosis. Our further study indicated that JNK and JNK-mediated BID cleavage may play an important role in synergistic effect between VELCADE and TRAIL.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2004
Accession Number
ADA427925

Entities

People

  • Honglin Li

Organizations

  • Ann & Robert H. Lurie Children's Hospital of Chicago

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biological Sciences
  • Biotechnology
  • Carrier Proteins
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Chemotherapeutic Agents
  • Epithelial Cells
  • Health Services
  • Inhibitors
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Resistance
  • Tissues

Fields of Study

  • Biology

Readers

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