Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in normal prostate epithelial cells

Alexandre Nesterov, Yuri Ivashchenko, Andrew S. Kraft

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

TRAIL is a pro-apoptotic cytokine believed to selectively kill cancer cells without harming normal ones. However, we found that in normal human prostate epithelial cells (PrEC) TRAIL is capable of inducing apoptosis as efficiently as in some tumor cell lines. At the same time, TRAIL did not cause apoptosis in several other human primary cell lines: Aorta smooth muscle cells, foreskin fibroblasts, and umbilical vein endothelial cells. Compared to these primary cells, PrEC were found to contain significantly fewer TRAIL receptors DcR1 and DcR2 which are not capable of conducting the apoptotic signal. This result suggests that the unusual sensitivity of PrEC to TRAIL may result from their deficiency in anti-apoptotic decoy receptors. The protein synthesis inhibitor cycloheximide significantly enhanced TRAIL toxicity toward PrEC as measured by tetrazolium conversion but had little or no effect on other TRAIL-induced apoptotic responses. Although cycloheximide did not further accelerate the processing of caspases 3 and 8, it significantly enhanced cleavage of the caspase 3 substrate gelsolin, indicating that in PrEC a protein(s) with a short half-life may inhibit the activity of the executioner caspases toward specific substrates. As the majority of prostate cancers are derived from epithelial cells, our data suggest the possibility that TRAIL could be a useful treatment for the early stages of prostate cancer.

Original languageEnglish (US)
Pages (from-to)1135-1140
Number of pages6
JournalOncogene
Volume21
Issue number7
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Human
  • Primary
  • Prostate
  • TRAIL

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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