PMID- 19794825
OWN - NLM
STAT- MEDLINE
DCOM- 20091209
LR  - 20211020
IS  - 1110-7251 (Electronic)
IS  - 1110-7243 (Print)
IS  - 1110-7243 (Linking)
VI  - 2009
DP  - 2009
TI  - LAS0811: from combinatorial chemistry to activation of antioxidant response 
      element.
PG  - 420194
LID - 10.1155/2009/420194 [doi]
LID - 420194
AB  - The antioxidant response element (ARE) and its transcription factor, nuclear 
      factor-erythroid 2 p45-related factor 2 (Nrf2), are potential targets for cancer 
      chemoprevention. We sought to screen small molecules synthesized with 
      combinatorial chemistry for activation of ARE. By high-throughput screening of 
      9400 small molecules from 10 combinatorial chemical libraries using HepG2 cells 
      with an ARE-driven reporter, we have identified a novel small molecule, 
      1,2-dimethoxy-4,5-dinitrobenzene (LAS0811), as an activator of the ARE. LAS0811 
      upregulated the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1), a 
      representative antioxidative enzyme regulated by ARE. It enhanced production of 
      an endogenous reducing agent, glutathione (GSH). In addition, LAS0811 induced 
      expression of heme oxygenase 1 (HO1), which is an ARE-regulated enzyme with 
      anti-inflammatory activity. Furthermore, LAS0811 reduced cell death due to the 
      cytotoxic stress of a strong oxidant, t-butyl hydroperoxide (t-BOOH). 
      Mechanistically, LAS0811 upregulated the expression of Nrf2 and promoted its 
      translocation into the nuclei leading to subsequent ARE activation. Taken 
      together, LAS0811 is a novel activator of the ARE and its associated detoxifying 
      genes and, thus, a potential agent for cancer chemoprevention.
FAU - Zhu, Ming
AU  - Zhu M
AD  - Division of Hematology/Oncology, Department of Internal Medicine, UC-Davis Cancer 
      Center, University of California-Davis, 4501 X Street, Sacramento, CA 95817, USA.
FAU - Baek, Hyounggee
AU  - Baek H
FAU - Liu, Ruiwu
AU  - Liu R
FAU - Song, Aimin
AU  - Song A
FAU - Lam, Kit
AU  - Lam K
FAU - Lau, Derick
AU  - Lau D
LA  - eng
GR  - UL1 RR024146/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090924
PL  - United States
TA  - J Biomed Biotechnol
JT  - Journal of biomedicine & biotechnology
JID - 101135740
RN  - 0 (Antioxidants)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
SB  - IM
MH  - Antioxidants/chemistry/metabolism
MH  - Combinatorial Chemistry Techniques/*methods
MH  - Drug Delivery Systems/methods
MH  - *Drug Design
MH  - Hep G2 Cells
MH  - Humans
MH  - NF-E2-Related Factor 2/*chemistry/genetics/*metabolism
MH  - Response Elements/*physiology
MH  - Structure-Activity Relationship
MH  - Transcriptional Activation/*physiology
PMC - PMC2753787
EDAT- 2009/10/02 06:00
MHDA- 2009/12/16 06:00
PMCR- 2009/09/24
CRDT- 2009/10/02 06:00
PHST- 2009/05/06 00:00 [received]
PHST- 2009/07/01 00:00 [revised]
PHST- 2009/07/07 00:00 [accepted]
PHST- 2009/10/02 06:00 [entrez]
PHST- 2009/10/02 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2009/09/24 00:00 [pmc-release]
AID - 10.1155/2009/420194 [doi]
PST - ppublish
SO  - J Biomed Biotechnol. 2009;2009:420194. doi: 10.1155/2009/420194. Epub 2009 Sep 
      24.