Apoptosis-induced by TRAIL AND TNF-alpha in human multiple myeloma cells is not blocked by BCL-2

Cytokine. 1999 Dec;11(12):1010-9. doi: 10.1006/cyto.1999.0536.

Abstract

TRAIL, the ligand for the newly discovered DR-4 and DR-5 receptor is a member of the tumour necrosis factor (TNF) family of death signal tranduction proteins with a mechanism of cell death, similar to the Fas and Fas ligand (Fas-L) system. Here, we provide first time evidence that TRAIL and TNF-alpha are potent inducers of apoptosis in multiple myeloma (MM) cell lines and freshly isolated myeloma cells. TRAIL effectively induced extensive apoptosis in 8226 and ARP-1 MM cells in a time- and dose-dependent manner reaching 80% within 48 h of treatment with a dose of 160 ng/ml. Bcl-2 transfected 8226 and ARP-1 cells were equally sensitive to apoptosis by TRAIL. Apoptosis with TNFalpha, reached >60% within 48 h of treatment with a dose of 160 ng/ml. In addition to MM cell lines, freshly isolated, flow-sorted myeloma cells from 8 different MM patients expressing variable levels of bcl-2 were equally sensitive to both TRAIL and TNF-alpha. We have previously shown that anti-Fas-induced apoptosis is not blocked by endogenous or ectopic bcl-2 in MM cell lines. Here we extend our observation with Fas to include TNF-alpha and TRAIL to the apoptotic signals that are not be blocked by bcl-2, in MM cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins
  • Humans
  • Ligands
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / pharmacology
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Apoptosis Regulatory Proteins
  • Ligands
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha