PMID- 19124248
OWN - NLM
STAT- MEDLINE
DCOM- 20090415
LR  - 20090203
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 17
IP  - 3
DP  - 2009 Feb 1
TI  - Death receptor 5 targeting activity-guided isolation of isoflavones from 
      Millettia brandisiana and Ardisia colorata and evaluation of ability to induce 
      TRAIL-mediated apoptosis.
PG  - 1181-6
LID - 10.1016/j.bmc.2008.12.033 [doi]
AB  - Death receptor 5 (DR5) is an apoptosis-inducing membrane receptor for TNF-related 
      apoptosis-inducing ligand (TRAIL). On screening for compounds that enhance DR5 
      expression using a luciferase assay with DLD-1/SacI, we previously identified 
      4'-demethyltoxicarol isoflavone (1) isolated from the leaves of Millettia 
      brandisiana. In this study, we revealed that 1 sensitized TRAIL-resistant human 
      gastric adenocarcinoma (AGS) cells to TRAIL-induced apoptosis by up-regulating 
      the expression of DR5. 1 induced DR5 expression at both the mRNA and protein 
      level. A human recombinant DR5/Fc chimera remarkably inhibited 1-induced 
      apoptosis. These results suggest that the enhancement of DR5 expression by 1 was 
      critical to the cell death. Furthermore, a MeOH extract of the bark of Ardisia 
      colorata markedly enhanced DR5 activity in this screening system. Bioassay-guided 
      fractionation of A. colorata led to the isolation and identification of a new 
      isoflavone, coloratanin A (3), together with ten known compounds. The chemical 
      structure of the new compound was elucidated on the basis of a spectroscopic 
      analysis.
FAU - Kikuchi, Hiroyuki
AU  - Kikuchi H
AD  - Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, 
      Inage-ku, Chiba 263-8522, Japan.
FAU - Ohtsuki, Takashi
AU  - Ohtsuki T
FAU - Koyano, Takashi
AU  - Koyano T
FAU - Kowithayakorn, Thaworn
AU  - Kowithayakorn T
FAU - Sakai, Toshiyuki
AU  - Sakai T
FAU - Ishibashi, Masami
AU  - Ishibashi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081224
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Isoflavones)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
SB  - IM
MH  - *Apoptosis
MH  - Ardisia/*chemistry
MH  - Cell Line, Tumor
MH  - Humans
MH  - Isoflavones/chemistry/isolation & purification/*pharmacology
MH  - Millettia/*chemistry
MH  - Plant Bark/chemistry
MH  - Plant Leaves/chemistry
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand/*pharmacology
MH  - Up-Regulation
EDAT- 2009/01/07 09:00
MHDA- 2009/04/16 09:00
CRDT- 2009/01/07 09:00
PHST- 2008/11/11 00:00 [received]
PHST- 2008/12/11 00:00 [revised]
PHST- 2008/12/13 00:00 [accepted]
PHST- 2009/01/07 09:00 [entrez]
PHST- 2009/01/07 09:00 [pubmed]
PHST- 2009/04/16 09:00 [medline]
AID - S0968-0896(08)01215-7 [pii]
AID - 10.1016/j.bmc.2008.12.033 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2009 Feb 1;17(3):1181-6. doi: 10.1016/j.bmc.2008.12.033. Epub 
      2008 Dec 24.