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Title | Suppression of RelA/p65 transactivation activity by a lignoid manassantin isolated from Saururus chinensis |
Authors | Jeong-Hyung Lee; B Y Hwang; Kyung Sook Kim; Jeong Beom Nam; Young-Soo Hong; Jung Joon Lee |
Publisher | Elsevier |
Issue Date | 2003 |
Citation | Biochemical Pharmacology, vol. 66, no. 10, pp. 1925-1933 |
Keywords | apoptosis; lignoids; NF-κB; RelA/p65; saururus chinensis; transactivation; DNA; I kappa B alpha; immunoglobulin enhancer binding protein; lipopolysaccharide |
Abstract | In our search for NF-κB inhibitors from natural resources, we have previously identified two structurally related dilignans, manassantin A and B as specific inhibitors of NF-κB 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-κB activation by the suppression of transciptional activity of RelA/p65 subunit of NF-κB. These compounds significantly inhibited the induced expression of NF-κB reporter gene by LPS or TNF-α in a dose-dependent manner. However, these compounds did not prevent the DNA-binding activity of NF-κB assessed by electrophoretic mobility shift assay as well as the induced-degradation of IκB-α protein by LPS or TNF-α. Further analysis revealed that manassantins A and B dose-dependently suppressed not only the induced NF-κB activation by overexpression of RelA/p65, but also transactivation activity of RelA/p65. Furthermore, treatment of cells with these compounds prevented the TNF-α-induced expression of anti-apoptotic NF-κB target genes Bfl-1/A1, a prosurvival Bcl-2 homologue, and resulted in sensitizing HT-1080 cells to TNF-α-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-κB-dependent pathological condition such as inflammation and cancer. |
ISSN | 0006-2952 |
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Registered Date |
2019-05-02 |
