Regulation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Burkitt's lymphoma cell lines

Br J Haematol. 2003 Jul;122(1):61-9. doi: 10.1046/j.1365-2141.2003.04424.x.

Abstract

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in sensitive cells and may be suitable for novel anti-cancer therapies aimed at inducing apoptosis via the activation of TRAIL receptors on malignant cells. Here we have characterized the TRAIL sensitivity of a panel of Burkitt's lymphoma (BL) cell lines. Overall, 5/12 BL cell lines and 1/2 lymphoblastoid cell lines were sensitive to TRAIL-induced apoptosis, although only one BL cell line approached the sensitivity of Jurkat cells, a widely used model for TRAIL-induced apoptosis. Whereas, 4/5 of the Epstein-Barr virus (EBV)-negative cell lines were TRAIL sensitive, only 1/7 EBV-positive BL cell lines were TRAIL sensitive. However, isogenic BL cell lines with different EBV status were not differently sensitive to TRAIL, indicating that EBV is not a major determinant of TRAIL sensitivity. All cell lines expressed the death receptor (DR)5 TRAIL receptor, whereas expression of DR4 was more variable. Differences in the expression of downstream signalling molecules [Fas-associated death domain protein (FADD), caspase 8] and inhibitors [decoy receptor 1 (DcR1), cellular FLICE-like inhibitory protein (c-FLIP)] did not correlate with TRAIL sensitivity. Therefore, a subset of BL cell lines are sensitive to TRAIL-induced apoptosis, however, the molecular mechanism that determines responsiveness remains to be identified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins
  • Burkitt Lymphoma / metabolism
  • Burkitt Lymphoma / pathology*
  • Burkitt Lymphoma / virology
  • Cisplatin / pharmacology
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Membrane Glycoproteins / pharmacology*
  • Neoplasm Proteins / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Cisplatin