LAS0811 : From Combinatorial Chemistry to Activation of Antioxidant Response Element
Joint Authors
Zhu, Ming
Lam, Kit S.
Lau, Derick
Baek, Hyounggee
Liu, Ruiwu
Song, Aimin
Source
Journal of Biomedicine and Biotechnology
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2009-09-24
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Zhu, Ming& Baek, Hyounggee& Liu, Ruiwu& Song, Aimin& Lam, Kit S.& Lau, Derick. 2009. LAS0811 : From Combinatorial Chemistry to Activation of Antioxidant Response Element. Journal of Biomedicine and Biotechnology،Vol. 2009, no. 2009, pp.1-8.
https://search.emarefa.net/detail/BIM-470800
Modern Language Association (MLA)
Zhu, Ming…[et al.]. LAS0811 : From Combinatorial Chemistry to Activation of Antioxidant Response Element. Journal of Biomedicine and Biotechnology No. 2009 (2009), pp.1-8.
https://search.emarefa.net/detail/BIM-470800
American Medical Association (AMA)
Zhu, Ming& Baek, Hyounggee& Liu, Ruiwu& Song, Aimin& Lam, Kit S.& Lau, Derick. LAS0811 : From Combinatorial Chemistry to Activation of Antioxidant Response Element. Journal of Biomedicine and Biotechnology. 2009. Vol. 2009, no. 2009, pp.1-8.
https://search.emarefa.net/detail/BIM-470800
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-470800