Mitochondria from TRAIL-resistant prostate cancer cells are capable of responding to apoptotic stimuli

Yayun Liang, Manal A. Eid, Ronald W. Lewis, M. Vijay Kumar

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

TNFα-related apoptosis inducing ligand (TRAIL) has been shown to induce apoptosis in prostate cancer cells. However, some prostate cancer cells, such as LNCaP are resistant to TRAIL. In addition to the involvement of several pathways in the TRAIL-resistance of LNCaP, it has been shown that mitochondrial response to TRIAL is low in these cells. Therefore, in this study, using in vitro cell free and reconstitution models, we have demonstrated that mitochondria from these cells are capable of responding to apoptotic stimuli. Furthermore, experiments to determine the influence of cytochrome c on apoptotic response noted that incubation of cytosol with exogenous cytochrome c induced truncation of Bid. We have demonstrated that truncation of Bid by exogenous cytochrome c is mediated through the activation of caspases-9 and -3. Incubation of cytosol with recombinant caspases-9 and -3 in the absence or presence of inhibitors showed that activation of caspase-9, leading to the activation of caspase-3 was necessary for the truncation of Bid. Published results indicate that in apoptotic cells cytochrome c is released from the mitochondria in two installments, an early small amount and a late larger amount. Our results suggest that the initial release of cytochrome generates tBid that is capable of translocation into the mitochondria causing further release of cytochrome c. Thus, in addition to providing functional explanation for the biphasic release of cytochrome c from mitochondria, we demonstrate the presence of a feedback amplification of mitochondrial apoptotic signal.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalCellular Signalling
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2005

Keywords

  • Apoptosis
  • Bid
  • Caspases
  • Cytochrome c
  • Mitochondria
  • Prostate cancer

ASJC Scopus subject areas

  • Cell Biology

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