PMID- 15138489
OWN - NLM
STAT- MEDLINE
DCOM- 20040616
LR  - 20181113
IS  - 0007-0920 (Print)
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Linking)
VI  - 90
IP  - 10
DP  - 2004 May 17
TI  - The anticancer drug mithramycin A sensitises tumour cells to apoptosis induced by 
      tumour necrosis factor (TNF).
PG  - 2025-31
AB  - In this report we show that mithramycin considerably increases the direct 
      cytotoxic effect of tumour necrosis factor (TNF) on tumour cells in vitro. 
      Sensitisation to TNF-induced apoptosis was prevented by the broad caspase 
      inhibitor zVAD-fmk, whereas overexpression of Bcl-2 had no effect. Mithramycin 
      also potentiated cell death induced by Fas agonistic antibodies. In contrast, 
      mithramycin reduced the percentage of cells undergoing apoptosis due to factor 
      withdrawal. TNF-induced activation of NF-kappaB (NF-kappaB)-dependent gene 
      expression was not modulated by mithramycin treatment. Concomitantly with the 
      increased sensitivity, the protein level of the short-spliced cFLIP variant was 
      downregulated. These results indicate that mithramycin enhances TNF-induced cell 
      death in an NF-kappaB-independent manner, and suggest that the Fas-associated 
      death domain protein plays a crucial role in the TNF-sensitising effect of 
      mithramycin.
FAU - Duverger, V
AU  - Duverger V
AD  - EiRx Therapeutics Ltd, 2800 Cork Airport Business Park, Kinsale Road, Cork, 
      Ireland.
FAU - Murphy, A-M
AU  - Murphy AM
FAU - Sheehan, D
AU  - Sheehan D
FAU - England, K
AU  - England K
FAU - Cotter, T G
AU  - Cotter TG
FAU - Hayes, I
AU  - Hayes I
FAU - Murphy, F J
AU  - Murphy FJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - 97666-60-9 (mithramycin A)
RN  - NIJ123W41V (Plicamycin)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Apoptosis/*drug effects
MH  - Carrier Proteins/*pharmacology
MH  - Drug Resistance, Neoplasm
MH  - Fas-Associated Death Domain Protein
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Leukemia, Erythroblastic, Acute/pathology
MH  - Leukemia, Promyelocytic, Acute/pathology
MH  - Plicamycin/*analogs & derivatives/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - fas Receptor
PMC - PMC2409467
EDAT- 2004/05/13 05:00
MHDA- 2004/06/17 05:00
PMCR- 2005/04/20
CRDT- 2004/05/13 05:00
PHST- 2004/05/13 05:00 [pubmed]
PHST- 2004/06/17 05:00 [medline]
PHST- 2004/05/13 05:00 [entrez]
PHST- 2005/04/20 00:00 [pmc-release]
AID - 6601824 [pii]
AID - 10.1038/sj.bjc.6601824 [doi]
PST - ppublish
SO  - Br J Cancer. 2004 May 17;90(10):2025-31. doi: 10.1038/sj.bjc.6601824.