PMID- 16007131
OWN - NLM
STAT- MEDLINE
DCOM- 20051207
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 24
IP  - 48
DP  - 2005 Nov 3
TI  - Luteolin induces apoptosis via death receptor 5 upregulation in human malignant 
      tumor cells.
PG  - 7180-9
AB  - Luteolin, a naturally occurring flavonoid, induces apoptosis in various cancer 
      cells. Little is known however concerning the underlying molecular mechanisms 
      responsible for this activity. In this report, we reveal a novel mechanism by 
      which luteolin-induced apoptosis occurs, and show for the first time that the 
      apoptosis by luteolin is mediated through death receptor 5 (DR5) upregulation. 
      Luteolin markedly induced the expression of DR5, along with Bcl-2-interacting 
      domain cleavage and the activation of caspase-8, -10, -9 and -3. In addition, 
      suppression of DR5 expression with siRNA efficiently reduced luteolin-induced 
      caspase activation and apoptosis. Human recombinant DR5/Fc also inhibited 
      luteolin-induced apoptosis. On the other hand, luteolin induced neither DR5 
      protein expression nor apoptosis in normal human peripheral blood mononuclear 
      cells. These results suggest that DR5 induced by luteolin plays a role in 
      luteolin-induced apoptosis, and raises the possibility that treatment with 
      luteolin might be promising as a new therapy against cancer.
CI  - Oncogene (2005) 24, 7180-7189. doi:10.1038/sj.onc.1208874; published online 11 
      July 2005.
FAU - Horinaka, Mano
AU  - Horinaka M
AD  - Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical 
      Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, 
      Kamigyo-ku, Kyoto 602-8566, Japan.
FAU - Yoshida, Tatsushi
AU  - Yoshida T
FAU - Shiraishi, Takumi
AU  - Shiraishi T
FAU - Nakata, Susumu
AU  - Nakata S
FAU - Wakada, Miki
AU  - Wakada M
FAU - Nakanishi, Ryoko
AU  - Nakanishi R
FAU - Nishino, Hoyoku
AU  - Nishino H
FAU - Matsui, Hiroshi
AU  - Matsui H
FAU - Sakai, Toshiyuki
AU  - Sakai T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (BH3 Interacting Domain Death Agonist Protein)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TNFRSF10A protein, human)
RN  - 0 (TNFRSF10B protein, human)
RN  - EC 1.13.12.- (Luciferases)
RN  - KUX1ZNC9J2 (Luteolin)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - BH3 Interacting Domain Death Agonist Protein/metabolism
MH  - Blotting, Western
MH  - Caspase Inhibitors
MH  - Cell Line, Tumor
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Luciferases/metabolism
MH  - Luteolin/*pharmacology
MH  - Male
MH  - Promoter Regions, Genetic
MH  - Prostatic Neoplasms/pathology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand
MH  - Receptors, Tumor Necrosis Factor/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Up-Regulation/*drug effects
EDAT- 2005/07/12 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/07/12 09:00
PHST- 2005/07/12 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/07/12 09:00 [entrez]
AID - 1208874 [pii]
AID - 10.1038/sj.onc.1208874 [doi]
PST - ppublish
SO  - Oncogene. 2005 Nov 3;24(48):7180-9. doi: 10.1038/sj.onc.1208874.