PMID- 14751507
OWN - NLM
STAT- MEDLINE
DCOM- 20040308
LR  - 20190708
IS  - 0360-3016 (Print)
IS  - 0360-3016 (Linking)
VI  - 58
IP  - 2
DP  - 2004 Feb 1
TI  - Influence of hypoxia on TRAIL-induced apoptosis in tumor cells.
PG  - 386-96
AB  - PURPOSE: Tumor hypoxia reduces the efficacy of radiotherapy, many types of 
      chemotherapy, and tumor necrosis factor-alpha (TNF-alpha). TRAIL 
      (TNF-alpha-related apoptosis-inducing ligand) is a ligand for death receptors of 
      the TNF superfamily shown to be selectively toxic for tumor cells and thereby a 
      promising antineoplastic tool. The impact of hypoxia on TRAIL-induced apoptosis 
      was examined in this study. METHODS AND MATERIALS: Apoptosis induction and growth 
      rates of various tumor cell lines under hypoxia were evaluated in vitro. 
      Biologically effective induction of hypoxia was verified by determination of 
      hypoxia-inducible factor-1 (HIF-1) activation. The efficacy of TRAIL- and 
      radiation-induced apoptosis under different oxygen conditions was quantified in 
      vitro. The impact of Bcl-2 on TRAIL-induced apoptosis under hypoxia or normoxia 
      was evaluated by comparing cells expressing Bcl-2 with a vector control. RESULTS: 
      Moderate hypoxia caused no growth retardation or apoptosis, but led to activation 
      of HIF-1 as a prerequisite of hypoxic gene induction. Cellular responses to TRAIL 
      differed considerably among the cell lines tested. Hypoxia reduced 
      radiation-induced, but not TRAIL-induced, apoptosis in the tested cell lines. 
      Hypoxia did not induce Bcl-2 expression. Bcl-2 had a minor impact on the efficacy 
      of TRAIL-induced apoptosis. CONCLUSION: Taken together, the data indicate that 
      TRAIL is clearly effective under conditions of proven hypoxia.
FAU - Weinmann, Martin
AU  - Weinmann M
AD  - Department of Radiation Oncology, University of Tubingen, Hoppe-Seylerstrasse 3, 
      72076 Tubingen, Germany.
FAU - Marini, Patrizia
AU  - Marini P
FAU - Jendrossek, Verena
AU  - Jendrossek V
FAU - Betsch, Angelika
AU  - Betsch A
FAU - Goecke, Barbara
AU  - Goecke B
FAU - Budach, Wilfried
AU  - Budach W
FAU - Belka, Claus
AU  - Belka C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Radiat Oncol Biol Phys
JT  - International journal of radiation oncology, biology, physics
JID - 7603616
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*physiology
MH  - Apoptosis Regulatory Proteins
MH  - Caspase 8
MH  - Caspases/metabolism
MH  - Cell Hypoxia/*physiology
MH  - Cell Line, Tumor/drug effects/radiation effects
MH  - Cell Nucleus/metabolism
MH  - DNA/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Drug Screening Assays, Antitumor
MH  - Enzyme Activation
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Jurkat Cells/drug effects/radiation effects
MH  - Membrane Glycoproteins/*pharmacology
MH  - Nuclear Proteins/*metabolism
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - *Transcription Factors
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2004/01/31 05:00
MHDA- 2004/03/09 05:00
CRDT- 2004/01/31 05:00
PHST- 2004/01/31 05:00 [pubmed]
PHST- 2004/03/09 05:00 [medline]
PHST- 2004/01/31 05:00 [entrez]
AID - S0360301603019916 [pii]
AID - 10.1016/j.ijrobp.2003.09.052 [doi]
PST - ppublish
SO  - Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):386-96. doi: 
      10.1016/j.ijrobp.2003.09.052.