Abstract：
:In our search for NF-kappaB inhibitors from natural resources, we have previously identified two structurally related dilignans, manassantin A and B as specific inhibitors of NF-kappaB activation from Saururus chinensis. However, their molecular mechanism of action remains unclear. We here demonstrate that manassantins A and B are potent inhibitors of NF-kappaB activation by the suppression of transciptional activity of RelA/p65 subunit of NF-kappaB. These compounds significantly inhibited the induced expression of NF-kappaB reporter gene by LPS or TNF-alpha in a dose-dependent manner. However, these compounds did not prevent the DNA-binding activity of NF-kappaB assessed by electrophoretic mobility shift assay as well as the induced-degradation of IkappaB-alpha protein by LPS or TNF-alpha. Further analysis revealed that manassantins A and B dose-dependently suppressed not only the induced NF-kappaB activation by overexpression of RelA/p65, but also transactivation activity of RelA/p65. Furthermore, treatment of cells with these compounds prevented the TNF-alpha-induced expression of anti-apoptotic NF-kappaB target genes Bfl-1/A1, a prosurvival Bcl-2 homologue, and resulted in sensitizing HT-1080 cells to TNF-alpha-induced cell death. Similarly, these compounds also suppressed the LPS-induced inducible nitric oxide synthase expression and nitric oxide production. Taken together, manassantins A and B could be valuable candidate for the intervention of NF-kappaB-dependent pathological condition such as inflammation and cancer.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Lee JH,Hwang BY,Kim KS,Nam JB,Hong YS,Lee JJdoi
10.1016/s0006-2952(03)00553-7subject
Has Abstractpub_date
2003-11-15 00:00:00pages
1925-33issue
10eissn
0006-2952issn
1873-2968pii
S0006295203005537journal_volume
66pub_type
杂志文章abstract：:A comparison of the effects of various phosphodiesterase (PDE) inhibitors upon cellular cAMP levels was undertaken in human neuroblastoma SH-SY5Y cells. When inhibitors such as rolipram and Ro 20 1724 (selective for the low Km cAMP-specific PDE) were used, cAMP levels were seen to rise dramatically under basal (< or =...
journal_title：Biochemical pharmacology
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pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2017.07.003
更新日期：2017-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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pub_type： 杂志文章,评审
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更新日期：2012-11-15 00:00:00
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90071-2
更新日期：1987-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1983-11-01 00:00:00
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pub_type： 杂志文章,评审
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pub_type： 杂志文章
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更新日期：2018-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00852-8
更新日期：2002-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00522-0
更新日期：2001-01-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90159-0
更新日期：1986-04-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90568-3
更新日期：1983-01-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90322-n
更新日期：1993-11-02 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(98)00227-5
更新日期：1999-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90640-x
更新日期：1987-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2016-11-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90169-w
更新日期：1993-02-24 00:00:00
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更新日期：1999-04-15 00:00:00
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journal_title：Biochemical pharmacology
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doi：10.1016/j.bcp.2004.11.026
更新日期：2005-03-01 00:00:00
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更新日期：2013-02-15 00:00:00
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journal_title：Biochemical pharmacology
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更新日期：1984-05-01 00:00:00
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journal_title：Biochemical pharmacology
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doi：10.1016/s0006-2952(01)00900-5
更新日期：2002-02-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00878-4
更新日期：2002-02-01 00:00:00
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更新日期：2012-02-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.09.009
更新日期：2010-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2017.06.113
更新日期：2017-11-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.01.036
更新日期：2018-04-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1988-10-01 00:00:00
