PMID- 20007968
OWN - NLM
STAT- MEDLINE
DCOM- 20100311
LR  - 20240317
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 8
DP  - 2010 Feb 19
TI  - CHM-1, a new vascular targeting agent, induces apoptosis of human umbilical vein 
      endothelial cells via p53-mediated death receptor 5 up-regulation.
PG  - 5497-506
LID - 10.1074/jbc.M109.036277 [doi]
AB  - CHM-1 (2'-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone) has been identified as 
      a potent antitumor agent in human hepatocellular carcinoma; however, its role in 
      tumor angiogenesis is unclear. This study investigated the effects of CHM-1 and 
      the mechanisms by which it exerts its antiangiogenic and vascular disrupting 
      properties. Using a xenograft model antitumor assay, we found that CHM-1 
      significantly inhibits tumor growth and microvessel formation. Flow cytometry, 
      immunofluorescence microscopy, and cell death enzyme-linked immunosorbent assay 
      kit revealed that CHM-1 inhibits growth of human umbilical vein endothelial cells 
      (HUVEC) by induction of apoptotic cell death in a concentration-dependent manner. 
      CHM-1 also suppresses HUVEC migration and capillary-like tube formation. We were 
      able to correlate CHM-1-induced apoptosis in HUVEC with the cleavage of 
      procaspase-3, -7, and -8, as well as with the cleavage of poly(ADP-ribose) 
      polymerase by Western blotting assay. Such sensitization was achieved through 
      up-regulation of death receptor 5 (DR5) but not DR4 or Fas. CHM-1 was also 
      capable of increasing the expression level of p53, and most importantly, the 
      induction of DR5 by CHM-1 was abolished by p53 small interfering RNA. Taken 
      together, the results of this study indicate that CHM-1 exhibits vascular 
      targeting activity associated with the induction of DR5-mediated endothelial cell 
      apoptosis through p53 up-regulation, which suggests its potential as an 
      antivascular and antitumor therapeutic agent.
FAU - Tsai, An-Chi
AU  - Tsai AC
AD  - Pharmacological Institute, College of Medicine, National Taiwan University, 
      Taipei 10051, Taiwan.
FAU - Pan, Shiow-Lin
AU  - Pan SL
FAU - Sun, Hui-Lung
AU  - Sun HL
FAU - Wang, Chih-Ya
AU  - Wang CY
FAU - Peng, Chieh-Yu
AU  - Peng CY
FAU - Wang, Shih-Wei
AU  - Wang SW
FAU - Chang, Ya-Ling
AU  - Chang YL
FAU - Kuo, Sheng-Chu
AU  - Kuo SC
FAU - Lee, Kuo-Hsiung
AU  - Lee KH
FAU - Teng, Che-Ming
AU  - Teng CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091211
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (2'-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Dioxoles)
RN  - 0 (FAS protein, human)
RN  - 0 (Quinolones)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (fas Receptor)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Caspases/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Dioxoles/pharmacology
MH  - Endothelial Cells/cytology/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Quinolones/pharmacology
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*biosynthesis
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Umbilical Veins/cytology/*metabolism
MH  - Up-Regulation/drug effects
MH  - Xenograft Model Antitumor Assays
MH  - fas Receptor/metabolism
PMC - PMC2820778
EDAT- 2009/12/17 06:00
MHDA- 2010/03/12 06:00
PMCR- 2011/02/19
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/03/12 06:00 [medline]
PHST- 2011/02/19 00:00 [pmc-release]
AID - S0021-9258(19)37528-3 [pii]
AID - M109.036277 [pii]
AID - 10.1074/jbc.M109.036277 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Feb 19;285(8):5497-506. doi: 10.1074/jbc.M109.036277. Epub 2009 
      Dec 11.