Apoptosis-induced by TRAIL and TNF-α in human multiple myeloma cells is not blocked by Bcl-2

Yair Gazitt, Paul Shaughnessy, Willi Montgomery

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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-α 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 TNFα, 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 mere equally sensitive to both TRAIL and TNF-α. 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-α and TRAIL to the apoptotic signals that are not be blocked by bcl-2, in MM cells.

Original languageEnglish (US)
Pages (from-to)1010-1019
Number of pages10
JournalCytokine
Volume11
Issue number12
DOIs
StatePublished - Dec 1999

Keywords

  • Apoptosis
  • Bcl-2
  • Fas
  • TNF
  • TRAIL

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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