Amorfrutin A inhibits TNF-α-induced NF-κB activation and NF-κB-regulated target gene products.
The nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, apoptosis, and angiogenesis. In our search for NF-κB inhibitors from natural resources, we identified amorfrutin A as an inhibitor of NF-κB activation from the fruits of Amorpha fruticosa L. In present study, this compound significantly inhibited the TNF-α-induced expression of NF-κB reporter gene. Further analysis revealed that amorfrutin A was a potent inhibitor of NF-κB activation by the suppression of TNF-α-induced inhibitor of κBα (IκBα) degradation, p65 nuclear translocation, and DNA-binding activity of NF-κB. We also demonstrated that pretreatment of cells with this compound prevented the TNF-α-induced expression of NF-κB target genes, such as antiapoptosis (cIAP-1 and FLIP), proliferation (COX-2 and cyclinD1), invasion (MMP-9), angiogenesis (VEGF), and major inflammatory cytokines (TNF-α, IL-8, and MCP1). Furthermore, our results suggest that amorfrutin A potentiates TNF-α-induced apoptosis. Taken together, amorfrutin A could be a valuable candidate for the intervention of NF-κB-dependent pathological conditions such as inflammation.
Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, Department of Chemistry, Yanbian University, Yanji 133002, Jilin Province, China.
Hui
H
Shi
Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China; Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China.
Juan
J
Ma
Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, Department of Chemistry, Yanbian University, Yanji 133002, Jilin Province, China.
Chunliu
C
Mi
Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, Department of Chemistry, Yanbian University, Yanji 133002, Jilin Province, China.
Jing
J
Li
Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China; Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China.
Fei
F
Wang
Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China. Electronic address: jjlee0908@gmail.com.
Jung Joon
JJ
Lee
Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China; Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China. Electronic address: xjjin@ybu.edu.cn.
Xuejun
X
Jin
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D007887:Fabaceae / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D012459:Salicylates / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D051034:Inhibitor of Apoptosis Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D012459:Salicylates; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C000597294:amorfrutin A; D019938:Cyclin D1; D051546:Cyclooxygenase 2; D019892:eIF-2 Kinase; D020780:Matrix Metalloproteinase 9
Amorfrutin A; Apoptosis; Inflammation; IκBα; Nuclear factor-κB (NF-κB)