PMID- 26654829
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20161230
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 130
IP  - 2
DP  - 2016 Feb
TI  - 4',6-Dihydroxy-4-methoxyisoaurone inhibits TNF-alpha-induced NF-kappaB activation and 
      expressions of NF-kappaB-regulated target gene products.
PG  - 43-50
LID - S1347-8613(15)00206-6 [pii]
LID - 10.1016/j.jphs.2015.10.002 [doi]
AB  - The nuclear factor-kappaB (NF-kappaB) transcription factors control many physiological 
      processes including inflammation, apoptosis, and angiogenesis. In our search for 
      NF-kappaB inhibitors from natural resources, we identified 
      4',6-dihydroxy-4-methoxyisoaurone (ISOA) as an inhibitor of NF-kappaB activation from 
      the seeds of Trichosanthes kirilowii. However, the mechanism by which ISOA 
      inhibits NF-kappaB activation is not fully understood. In the present study, we 
      demonstrated the effect of ISOA on NF-kappaB activation in TNF-alpha-stimulated HeLa 
      cells. This compound suppressed NF-kappaB activation through the inhibition of IkappaB 
      kinase (IKK) activation. ISOA also has an influence on upstream signaling of IKK 
      through the inhibition of expression of adaptor proteins, TNF receptor-associated 
      factor 2 (TRAF2) and receptor interacting protein 1 (RIP1). Consequently, ISOA 
      blocked the phosphorylation and degradation of the inhibitor of NF-kappaB alpha 
      (IkappaBalpha), and subsequent phosphorylation and nuclear translocation of p65. The 
      suppression of NF-kappaB activation by ISOA led to the down-regulation of target 
      genes involved in inflammation, proliferation, as well as potentiation of 
      TNF-alpha-induced apoptosis. Taken together, this study extends our understanding on 
      the mechanisms underlying the anti-inflammatory and anti-cancer activities of 
      ISOA. Our findings provide new insight into the molecular mechanisms and a 
      potential application of ISOA for inflammatory diseases as well as certain 
      cancers.
CI  - Copyright (c) 2015 The Authors. Production and hosting by Elsevier B.V. All rights 
      reserved.
FAU - Ma, Juan
AU  - Ma J
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, 
      Jilin Province, China; Molecular Cancer Research Center, Yanbian University, 
      Yanji 133002, Jilin Province, China.
FAU - Mi, Chunliu
AU  - Mi C
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, 
      Jilin Province, China; Molecular Cancer Research Center, Yanbian University, 
      Yanji 133002, Jilin Province, China.
FAU - Wang, Ke Si
AU  - Wang KS
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, 
      Jilin Province, China; Molecular Cancer Research Center, Yanbian University, 
      Yanji 133002, Jilin Province, China.
FAU - Lee, Jung Joon
AU  - Lee JJ
AD  - Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin 
      Province, China.
FAU - Jin, Xuejun
AU  - Jin X
AD  - Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, 
      Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, 
      Jilin Province, China; Molecular Cancer Research Center, Yanbian University, 
      Yanji 133002, Jilin Province, China. Electronic address: xjjin@ybu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151017
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (4',6-dihydroxy-4-methoxyisoaurone)
RN  - 0 (AGFG1 protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Pore Complex Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Sesquiterpenes)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/metabolism
MH  - Apoptosis/drug effects/genetics
MH  - Cell Proliferation/drug effects/genetics
MH  - Gene Expression/*drug effects/*genetics
MH  - HeLa Cells
MH  - Humans
MH  - I-kappa B Kinase/antagonists & inhibitors
MH  - Inflammation/drug therapy/genetics
MH  - NF-kappa B/*metabolism
MH  - Neoplasms/drug therapy/genetics
MH  - Nuclear Pore Complex Proteins/genetics/metabolism
MH  - Phosphorylation/drug effects
MH  - Phytotherapy
MH  - RNA-Binding Proteins/genetics/metabolism
MH  - Seeds/chemistry
MH  - Sesquiterpenes/isolation & purification/*pharmacology
MH  - TNF Receptor-Associated Factor 2/genetics/metabolism
MH  - Transcription Factor RelA/metabolism
MH  - Trichosanthes/chemistry
MH  - *Tumor Necrosis Factor-alpha
OTO - NOTNLM
OT  - 4',6-dihydroxy-4-methoxyisoaurone
OT  - Apoptosis
OT  - IkappaBalpha
OT  - NF-kappaB
OT  - p65
EDAT- 2015/12/15 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/12/15 06:00
PHST- 2015/02/21 00:00 [received]
PHST- 2015/09/27 00:00 [revised]
PHST- 2015/10/05 00:00 [accepted]
PHST- 2015/12/15 06:00 [entrez]
PHST- 2015/12/15 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - S1347-8613(15)00206-6 [pii]
AID - 10.1016/j.jphs.2015.10.002 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2016 Feb;130(2):43-50. doi: 10.1016/j.jphs.2015.10.002. Epub 
      2015 Oct 17.