PMID- 15130948
OWN - NLM
STAT- MEDLINE
DCOM- 20041004
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 104
IP  - 5
DP  - 2004 Sep 1
TI  - Molecular mechanism of violacein-mediated human leukemia cell death.
PG  - 1459-64
AB  - Violacein, a pigment isolated from Chromobacterium violaceum in the Amazon River, 
      presents diverse biologic properties and attracts interest as a consequence of 
      its antileukemic activity. Elucidation of the molecular mechanism mediating this 
      activity will provide further relevant information for understanding its effects 
      on the cellular physiology of untransformed cells and for considering its 
      possible clinical application. Here, we show that violacein causes apoptosis in 
      HL60 leukemic cells but is ineffective in this respect in other types of leukemia 
      cells or in normal human lymphocytes and monocytes. Violacein cytotoxicity in 
      HL60 cells was preceded by activation of caspase 8, transcription of nuclear 
      factor kappaB (NF-kappaB) target genes, and p38 mitogen-activated protein (MAP) 
      kinase activation. Thus, violacein effects resemble tumor necrosis factor alpha 
      (TNF-alpha) signal transduction in these cells. Accordingly, infliximab, an 
      antibody that antagonizes TNF-alpha-induced signaling abolished the biologic 
      activity of violacein. Moreover, violacein directly activated TNF receptor 1 
      signaling, because a violacein-dependent association of TNF receptor-associated 
      factor 2 (TRAF2) to this TNF receptor was observed in coimmunoprecipitation 
      experiments. Hence, violacein represents the first member of a novel class of 
      cytotoxic drugs mediating apoptosis of HL60 cells by way of the specific 
      activation of TNF receptor 1.
FAU - Ferreira, Carmen Verissima
AU  - Ferreira CV
AD  - Departamento de Bioquimica, Universidade Estadual de Campinas, Sao Paulo, Brazil.
FAU - Bos, Carina L
AU  - Bos CL
FAU - Versteeg, Henri H
AU  - Versteeg HH
FAU - Justo, Giselle Z
AU  - Justo GZ
FAU - Duran, Nelson
AU  - Duran N
FAU - Peppelenbosch, Maikel P
AU  - Peppelenbosch MP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040506
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Indoles)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (STAT2 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - QJH0DSQ3SG (violacein)
SB  - IM
MH  - Antigens, CD/metabolism
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Death/*drug effects
MH  - Cell Survival/drug effects
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - HL-60 Cells
MH  - Humans
MH  - Indoles/*pharmacology
MH  - K562 Cells
MH  - *Leukemia, Promyelocytic, Acute
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - STAT1 Transcription Factor
MH  - STAT2 Transcription Factor
MH  - Signal Transduction/drug effects
MH  - Trans-Activators/metabolism
MH  - U937 Cells
MH  - Up-Regulation/drug effects
EDAT- 2004/05/08 05:00
MHDA- 2004/10/05 09:00
CRDT- 2004/05/08 05:00
PHST- 2004/05/08 05:00 [pubmed]
PHST- 2004/10/05 09:00 [medline]
PHST- 2004/05/08 05:00 [entrez]
AID - S0006-4971(20)43489-5 [pii]
AID - 10.1182/blood-2004-02-0594 [doi]
PST - ppublish
SO  - Blood. 2004 Sep 1;104(5):1459-64. doi: 10.1182/blood-2004-02-0594. Epub 2004 May 
      6.