PMID- 19882112
OWN - NLM
STAT- MEDLINE
DCOM- 20100426
LR  - 20211018
IS  - 1573-7209 (Electronic)
IS  - 0969-6970 (Linking)
VI  - 12
IP  - 4
DP  - 2009
TI  - Anti-angiogenic actions of pyrrolidine dithiocarbamate, a nuclear factor kappa B 
      inhibitor.
PG  - 365-79
LID - 10.1007/s10456-009-9158-0 [doi]
AB  - Renal cell carcinomas (RCC) are a heterogeneous group of cancers that often 
      include angiogenesis as a key clinical and pathological hallmark. As the 
      transcription factor nuclear factor kappa B (NF-kappaB) has been identified as a 
      key promoter of angiogenesis, NF-kappaB inhibitors could serve as potential 
      anti-angiogenic agents. In this study, we tested the anti-angiogenic properties 
      of pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, using established 
      in vitro and ex vivo assays in human umbilical vein endothelial cells (HUVEC) and 
      human metastatic RCC cell lines (ACHN and SN12K1). In vitro, PDTC inhibited 
      proliferation, capillary tube formation, invasion and trans-differentiation of 
      HUVEC. Ex vivo, PDTC blocked vessel sprouting from aortic explants and disrupted 
      the integrity of pre-formed vessels. PDTC also inhibited the adhesion of HUVEC 
      and RCC cells to substratum and inhibited their invasion. PDTC inhibited 
      RCC-induced proliferation of HUVEC. Protein microarray demonstrated heterogenic 
      actions in each cell line: in HUVEC, epidermal growth factor was significantly 
      decreased; in ACHN, basic fibroblast growth factor, growth related oncogene, 
      interleukin-6, RANTES and monocyte chemoattractant protein-1 (MCP-1) were 
      significantly decreased; and in SN12K1, MCP-1 was upregulated. PDTC increased the 
      expression of the pro-angiogenic protein interleukin-8 in both RCC cell lines. 
      Expression of vascular endothelial growth factor (VEGF) was not significantly 
      altered, and exogenous VEGF had a neutral effect on in vitro angiogenesis of 
      HUVEC. Collectively, these data suggest that PDTC has some anti-angiogenic 
      properties, which may limit development and progression of RCC.
FAU - Morais, Christudas
AU  - Morais C
AD  - Department of Renal Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, 
      Australia. c.morais@uq.edu.au
FAU - Gobe, Glenda
AU  - Gobe G
FAU - Johnson, David W
AU  - Johnson DW
FAU - Healy, Helen
AU  - Healy H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091014
PL  - Germany
TA  - Angiogenesis
JT  - Angiogenesis
JID - 9814575
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Peptides)
RN  - 0 (SN50 peptide)
RN  - 0 (Thiocarbamates)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 135467-92-4 (prolinedithiocarbamate)
RN  - 9DLQ4CIU6V (Proline)
SB  - IM
MH  - Amino Acid Sequence
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Aorta/cytology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Renal Cell/pathology/secondary
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor/drug effects
MH  - Cell Transdifferentiation/drug effects
MH  - Cells, Cultured/cytology/drug effects
MH  - Endothelial Cells/cytology/*drug effects
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Kidney Neoplasms/pathology
MH  - Molecular Sequence Data
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Neoplasm Proteins/biosynthesis/genetics
MH  - Neovascularization, Pathologic/*drug therapy
MH  - Neovascularization, Physiologic/*drug effects
MH  - Organ Culture Techniques
MH  - Peptides/pharmacology
MH  - Proline/*analogs & derivatives/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thiocarbamates/*pharmacology
MH  - Umbilical Veins/cytology
MH  - Vascular Endothelial Growth Factor A/biosynthesis
EDAT- 2009/11/03 06:00
MHDA- 2010/04/27 06:00
CRDT- 2009/11/03 06:00
PHST- 2009/06/15 00:00 [received]
PHST- 2009/09/15 00:00 [accepted]
PHST- 2009/11/03 06:00 [entrez]
PHST- 2009/11/03 06:00 [pubmed]
PHST- 2010/04/27 06:00 [medline]
AID - 10.1007/s10456-009-9158-0 [doi]
PST - ppublish
SO  - Angiogenesis. 2009;12(4):365-79. doi: 10.1007/s10456-009-9158-0. Epub 2009 Oct 
      14.