PMID- 23261968
OWN - NLM
STAT- MEDLINE
DCOM- 20130805
LR  - 20130219
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 700
IP  - 1-3
DP  - 2013 Jan 30
TI  - Ethyl 3',4',5'-trimethoxythionocinnamate modulates NF-kappaB and Nrf2 transcription 
      factors.
PG  - 32-41
LID - S0014-2999(12)01009-6 [pii]
LID - 10.1016/j.ejphar.2012.12.004 [doi]
AB  - Recently, we identified a novel cinnamate analog, ethyl 
      3',4',5'-trimethoxythionocinnamate (ETMTC) as a potent inhibitor of cell adhesion 
      molecules (CAMs), such as intercellular adhesion molecule-1 (ICAM-1), vascular 
      cell adhesion molecule-1 (VCAM-1) and E-selectin. However, its mechanism of 
      action has not been elucidated so far. Since, nuclear factor-kappa B (NF-kappaB) is 
      the major transcription factor involved in the regulation of ICAM-1, VCAM-1 and 
      E-selectin expression, we determined the status of NF-kappaB activation in ETMTC 
      treated human endothelial cells. Here, we demonstrate that ETMTC inhibits 
      TNF-alpha-induced nuclear translocation and activation of NF-kappaB by inhibiting 
      phosphorylation and degradation of IkappaBalpha. The inhibition of IkappaBalpha phosphorylation 
      and degradation by ETMTC was found to be due to its ability to inhibit IkappaB kinase 
      activity. In addition, oxidative stress is known to regulate NF-kappaB activation 
      through TNF-alpha signaling cascade, therefore, we examined the effect of ETMTC on 
      TNF-alpha-induced reactive oxygen species generation. We observed that ETMTC 
      significantly inhibits TNF-alpha-induced reactive oxygen species generation in 
      endothelial cells. To further elucidate the anti-oxidant potential of ETMTC, we 
      examined its effect on induction of anti-oxidant genes viz. glutamate-cysteine 
      ligase, modifier subunit (GCLM), heme oxygenase-1 (HO1) and NAD (P)H:quinone 
      oxidoreductase 1 (NQO1) in human bronchial epithelial cells. Interestingly, ETMTC 
      significantly induces the anti-oxidant genes viz. GCLM, HO1 and NQO1 by 
      activating nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Thus, ETMTC 
      could be useful towards developing potent anti-inflammatory molecules.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Kumar, Sarvesh
AU  - Kumar S
AD  - Molecular Immunogenetics Laboratory, CSIR-Institute of Genomics and Integrative 
      Biology, Mall Road, Delhi 110007, India.
FAU - Singh, Brajendra K
AU  - Singh BK
FAU - Prasad, Ashok K
AU  - Prasad AK
FAU - Parmar, Virinder S
AU  - Parmar VS
FAU - Biswal, Shyam
AU  - Biswal S
FAU - Ghosh, Balaram
AU  - Ghosh B
LA  - eng
GR  - ES03819/ES/NIEHS NIH HHS/United States
GR  - P01ES018176/ES/NIEHS NIH HHS/United States
GR  - P50ES015903/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121220
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Cinnamates)
RN  - 0 (E-Selectin)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (ethyl 3',4',5'-trimethoxythionocinnamate)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cinnamates/*pharmacology
MH  - E-Selectin/genetics
MH  - Epithelial Cells/drug effects/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - I-kappa B Kinase/metabolism
MH  - Intercellular Adhesion Molecule-1/genetics
MH  - Intracellular Space/drug effects/metabolism
MH  - Kinetics
MH  - NF-E2-Related Factor 2/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Phosphorylation/drug effects
MH  - Proteolysis/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Transcription Factor RelA/metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Vascular Cell Adhesion Molecule-1/genetics
EDAT- 2012/12/25 06:00
MHDA- 2013/08/06 06:00
CRDT- 2012/12/25 06:00
PHST- 2012/04/28 00:00 [received]
PHST- 2012/12/06 00:00 [revised]
PHST- 2012/12/11 00:00 [accepted]
PHST- 2012/12/25 06:00 [entrez]
PHST- 2012/12/25 06:00 [pubmed]
PHST- 2013/08/06 06:00 [medline]
AID - S0014-2999(12)01009-6 [pii]
AID - 10.1016/j.ejphar.2012.12.004 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2013 Jan 30;700(1-3):32-41. doi: 10.1016/j.ejphar.2012.12.004. 
      Epub 2012 Dec 20.