Suppression of Bcl-2 messenger RNA production may mediate apoptosis after ionizing radiation, tumor necrosis factor alpha, and ceramide

Cancer Res. 1995 Mar 1;55(5):991-4.

Abstract

Recent studies have proposed that tumor necrosis factor alpha (TNF-alpha) and ionizing radiation induce apoptosis by activating hydrolysis of sphingomyelin to ceramide. Bcl-2 and a related gene, Bcl-X, inhibit several forms of apoptosis. Herein, we report that internucleosomal DNA fragmentation, characteristic of apoptosis and induced by ionizing radiation, is accompanied by concomitant decreases in Bcl-2 and Bcl-X mRNA levels in HL-60 and U-937 human leukemia cells. Apoptotic DNA fragmentation after exposure to TNF-alpha and C2-ceramide was also associated with down-regulation of Bcl-2 mRNA in HL-60 and U-937 cells, while Bcl-X mRNA production was unaffected. These results suggest that modulation of Bcl-2 gene expression may be a target for ceramide-mediated apoptosis following exposure to ionizing radiation and TNF-alpha. Changes in Bcl-2 expression may be the basis for the interactive killing observed between radiation and TNF-alpha in some human and tumor cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Apoptosis / radiation effects*
  • Base Sequence
  • Cell Death / drug effects
  • Cell Death / physiology
  • Ceramides / pharmacology*
  • Combined Modality Therapy
  • DNA Damage
  • DNA, Neoplasm / drug effects
  • DNA, Neoplasm / metabolism
  • DNA, Neoplasm / radiation effects
  • Down-Regulation
  • Gene Expression / drug effects
  • Gene Expression / radiation effects
  • Gene Expression Regulation, Leukemic
  • Humans
  • Leukemia / drug therapy
  • Leukemia / pathology
  • Leukemia / radiotherapy
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / drug effects
  • RNA, Messenger / radiation effects
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / radiation effects
  • Tumor Necrosis Factor-alpha / pharmacology*
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • Ceramides
  • DNA, Neoplasm
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • bcl-X Protein