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

Y Gazitt1, P Shaughnessy, W Montgomery

  • 1Department of Medicine/Hematology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, U S A.

Cytokine
|January 7, 2000
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TNF-alpha effectively induce apoptosis in multiple myeloma cells. These signals are not blocked by Bcl-2, offering potential therapeutic strategies.

Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • TRAIL is a TNF-family protein that induces apoptosis via DR-4/DR-5 receptors.
  • The Fas/Fas-L system also mediates apoptosis.
  • Bcl-2 is an anti-apoptotic protein implicated in cancer resistance.

Purpose of the Study:

  • To investigate the efficacy of TRAIL and TNF-alpha in inducing apoptosis in multiple myeloma (MM) cells.
  • To determine if Bcl-2 expression affects MM cell sensitivity to TRAIL and TNF-alpha.

Main Methods:

  • Treatment of MM cell lines (8226, ARP-1) and primary patient cells with TRAIL and TNF-alpha.
  • Dose- and time-dependent apoptosis assays.
  • Assessment of apoptosis in Bcl-2 transfected MM cells.
  • Flow-sorted primary myeloma cells from MM patients were used.

Main Results:

  • TRAIL induced apoptosis in MM cell lines in a time- and dose-dependent manner, reaching 80% at 160 ng/ml within 48h.
  • TNF-alpha induced >60% apoptosis in MM cell lines within 48h at 160 ng/ml.
  • Freshly isolated myeloma cells from 8 MM patients were sensitive to both TRAIL and TNF-alpha, irrespective of Bcl-2 levels.
  • Bcl-2 did not block TRAIL- or TNF-alpha-induced apoptosis in MM cells.

Conclusions:

  • TRAIL and TNF-alpha are potent inducers of apoptosis in multiple myeloma cell lines and primary cells.
  • Bcl-2 does not inhibit apoptosis induced by TRAIL or TNF-alpha in multiple myeloma.
  • These findings suggest TRAIL and TNF-alpha as promising therapeutic agents for multiple myeloma.

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