PMID- 15962302
OWN - NLM
STAT- MEDLINE
DCOM- 20051018
LR  - 20181201
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 95
IP  - 5
DP  - 2005 Aug 1
TI  - Arsenic trioxide (As2O3) inhibits invasion of HT1080 human fibrosarcoma cells: 
      role of nuclear factor-kappaB and reactive oxygen species.
PG  - 955-69
AB  - In order to define the role of As2O3 in regulating the tumor cell invasiveness, 
      the effects of As2O3 on secretion of matrix metalloproteinases (MMPs) and 
      urokinase plasminogen activator (uPA), and in vitro invasion of HT1080 human 
      fibrosarcoma cells were examined. As2O3 inhibited cell adhesion to the collagen 
      matrix in a concentration dependent manner, whereas the same treatment enhanced 
      cell to cell interaction. In addition, As2O3 inhibited migration and invasion of 
      HT1080 cells stimulated with phorbol 12-myristate 13-aceate (PMA), and suppressed 
      the expression of MMP-2, -9, membrane type-1 MMP, uPA, and uPA receptor (uPAR). 
      In contrast, As2O3 increased the expression of tissue inhibitor of 
      metalloproteinase (TIMP)-1 and PA inhibitor (PAI)-1, and reduced the MMP-2, -9, 
      and uPA promoter activity in the presence and absence of PMA. Furthermore, the 
      promoter stimulating and DNA binding activity of nuclear factor-kappaB 
      (NF-kappaB) was blocked by As2O3, whereas the activator protein-1 activity was 
      unchanged. Pretreatment of the cells with N-acetyl-L-cysteine (NAC) significantly 
      prevented suppression of MMPs and uPA secretion, DNA binding activity of 
      NF-kappaB, and in vitro invasion of HT1080 cells by As2O3, suggesting a role of 
      reactive oxygen species (ROS) in this process. These results suggest that As2O3 
      inhibits tumor cell invasion by modulating the MMPs/TIMPs and uPA/uPAR/PAI 
      systems of extracellular matrix (ECM) degradation. In addition, the generation of 
      ROS and subsequent suppression of NF-kappaB activity by As2O3 might partly be 
      responsible for the phenomena. Overall, As2O3 shows potent activity controlling 
      tumor cell invasiveness in vitro.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - Park, Myung-Jin
AU  - Park MJ
AD  - Laboratory of Cell Biology, Korea Institute of Radiological and Medical Sciences, 
      Seoul, Korea.
FAU - Lee, Jae-Young
AU  - Lee JY
FAU - Kwak, Hee-Jin
AU  - Kwak HJ
FAU - Park, Chang-Min
AU  - Park CM
FAU - Lee, Hyung-Chahn
AU  - Lee HC
FAU - Woo, Sang Hyeok
AU  - Woo SH
FAU - Jin, Hyun-Ok
AU  - Jin HO
FAU - Han, Chul-Ju
AU  - Han CJ
FAU - An, Sungkwan
AU  - An S
FAU - Lee, Seung-Hoon
AU  - Lee SH
FAU - Chung, Hee Yong
AU  - Chung HY
FAU - Park, In-Chul
AU  - Park IC
FAU - Hong, Seok-Il
AU  - Hong SI
FAU - Rhee, Chang Hun
AU  - Rhee CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Arsenicals)
RN  - 0 (NF-kappa B)
RN  - 0 (Oxides)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - S7V92P67HO (Arsenic Trioxide)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Arsenic Trioxide
MH  - Arsenicals/*pharmacology
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Adhesion/drug effects
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Electrophoretic Mobility Shift Assay
MH  - Fibrosarcoma/*metabolism/pathology
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Luciferases/metabolism
MH  - Matrix Metalloproteinase 2/metabolism
MH  - NF-kappa B/*metabolism
MH  - Neoplasm Invasiveness/*pathology
MH  - Oxides/*pharmacology
MH  - Plasminogen Activator Inhibitor 1/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - Tumor Cells, Cultured
MH  - Urokinase-Type Plasminogen Activator/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2005/06/18 09:00
MHDA- 2005/10/19 09:00
CRDT- 2005/06/18 09:00
PHST- 2005/06/18 09:00 [pubmed]
PHST- 2005/10/19 09:00 [medline]
PHST- 2005/06/18 09:00 [entrez]
AID - 10.1002/jcb.20452 [doi]
PST - ppublish
SO  - J Cell Biochem. 2005 Aug 1;95(5):955-69. doi: 10.1002/jcb.20452.