PMID- 21887462
OWN - NLM
STAT- MEDLINE
DCOM- 20120120
LR  - 20151119
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 40
IP  - 1
DP  - 2012 Jan
TI  - Bufotalin sensitizes death receptor-induced apoptosis via Bid- and 
      STAT1-dependent pathways.
PG  - 203-8
LID - 10.3892/ijo.2011.1182 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) and TNF-related apoptosis-inducing ligand 
      (TRAIL) are apoptosis-inducing ligands that stimulate death receptors. In this 
      study, we investigated the effects of bufotalin, a major compound in toad venom, 
      on sensitizing TNF-alpha and TRAIL-induced apoptosis of HeLa cells. Bufotalin 
      promoted death receptor-mediated cell death, especially TRAIL-induced apoptosis, 
      through activation of caspase-3 and PARP-1. Mitochondrial Bid-dependent pathway 
      was activated in TNF-alpha-induced cell death. Cotreatment of bufotalin with TRAIL 
      resulted in the downregulation of anti-apoptotic proteins, including Bcl-XL, 
      Mcl-1, survivin and XIAP, and the up-regulation of MAPKs and TRAIL receptor DR5. 
      In addition, phosphorylation of STAT1 was strongly inhibited by bufotalin. 
      Moreover, DR5 expression was induced by knocking down the STAT1 expression. 
      Moreover, the TRAIL-induced apoptotic response was promoted by STAT1 siRNA. Our 
      results demonstrated that bufotalin is a powerful sensitizer of death 
      receptor-induced apoptosis in cancer cells.
FAU - Waiwut, Pornthip
AU  - Waiwut P
AD  - Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of 
      Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
FAU - Inujima, Akiko
AU  - Inujima A
FAU - Inoue, Hiroki
AU  - Inoue H
FAU - Saiki, Ikuo
AU  - Saiki I
FAU - Sakurai, Hiroaki
AU  - Sakurai H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110901
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (BH3 Interacting Domain Death Agonist Protein)
RN  - 0 (BID protein, human)
RN  - 0 (Bufanolides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EGL9670I6P (bufotalin)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - BH3 Interacting Domain Death Agonist Protein/*metabolism
MH  - Bufanolides/*pharmacology
MH  - Drug Synergism
MH  - HeLa Cells
MH  - Humans
MH  - Phosphorylation/drug effects
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*biosynthesis/genetics
MH  - Recombinant Proteins/pharmacology
MH  - STAT1 Transcription Factor/*metabolism
MH  - Signal Transduction/drug effects
MH  - TNF-Related Apoptosis-Inducing Ligand/antagonists & inhibitors/pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2011/09/03 06:00
MHDA- 2012/01/21 06:00
CRDT- 2011/09/03 06:00
PHST- 2011/06/15 00:00 [received]
PHST- 2011/08/01 00:00 [accepted]
PHST- 2011/09/03 06:00 [entrez]
PHST- 2011/09/03 06:00 [pubmed]
PHST- 2012/01/21 06:00 [medline]
AID - 10.3892/ijo.2011.1182 [doi]
PST - ppublish
SO  - Int J Oncol. 2012 Jan;40(1):203-8. doi: 10.3892/ijo.2011.1182. Epub 2011 Sep 1.