Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor
Justicidin A (JA), a natural lignan, was isolated from the whole plant of Justicia procumbens, one of the most popular traditional Chinese medicines in China and Taiwan. Gene expression signatures of JA from human colorectal cancer HT-29 and hepatocellular carcinoma Hep 3B cells were used to query c...
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Format: | Article |
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Elsevier
2017-07-01
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Series: | Journal of Functional Foods |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464617302062 |
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author | Shen-Jeu Won Cheng-Hsin Yen Hao-Wen Hsieh Shao-Wei Chang Chun-Nan Lin Chi-Ying F. Huang Chun-Li Su |
author_facet | Shen-Jeu Won Cheng-Hsin Yen Hao-Wen Hsieh Shao-Wei Chang Chun-Nan Lin Chi-Ying F. Huang Chun-Li Su |
author_sort | Shen-Jeu Won |
collection | DOAJ |
description | Justicidin A (JA), a natural lignan, was isolated from the whole plant of Justicia procumbens, one of the most popular traditional Chinese medicines in China and Taiwan. Gene expression signatures of JA from human colorectal cancer HT-29 and hepatocellular carcinoma Hep 3B cells were used to query connectivity map. A NF-κB suppressor (15-delta prostaglandin J2) was predicted to display similar molecular action of JA. In JA-treated HT-29 cells, suppression of nuclear NF-κB expression and decrease of NF-κB DNA-binding activity were indeed observed. The classical pathway was involved in JA-induced inhibition of NF-κB, characterized by decreases in phosphorylation of AKT, IκB kinase (IKK)-β/IKK-α, and IκB-α. Furthermore, JA caused significant translocation of apoptosis-inducing factor and endonuclease G, caspase-independent apoptotic signaling molecules, from the mitochondrial to the nuclei. Our data suggest anti-inflammatory and cytotoxic mechanisms of JA, and using gene expression signatures to identify novel molecular actions of phytochemicals is an effective approach. |
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id | doaj.art-d4196d5b01cf4a829f021c2d72c7a901 |
institution | Directory Open Access Journal |
issn | 1756-4646 |
language | English |
last_indexed | 2024-12-20T01:16:19Z |
publishDate | 2017-07-01 |
publisher | Elsevier |
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series | Journal of Functional Foods |
spelling | doaj.art-d4196d5b01cf4a829f021c2d72c7a9012022-12-21T19:58:34ZengElsevierJournal of Functional Foods1756-46462017-07-01346876Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressorShen-Jeu Won0Cheng-Hsin Yen1Hao-Wen Hsieh2Shao-Wei Chang3Chun-Nan Lin4Chi-Ying F. Huang5Chun-Li Su6Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanDepartment of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei 112, TaiwanInstitute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, TaiwanSchool of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan; Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan; Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Corresponding author at: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan.Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan; Corresponding author at: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan.Justicidin A (JA), a natural lignan, was isolated from the whole plant of Justicia procumbens, one of the most popular traditional Chinese medicines in China and Taiwan. Gene expression signatures of JA from human colorectal cancer HT-29 and hepatocellular carcinoma Hep 3B cells were used to query connectivity map. A NF-κB suppressor (15-delta prostaglandin J2) was predicted to display similar molecular action of JA. In JA-treated HT-29 cells, suppression of nuclear NF-κB expression and decrease of NF-κB DNA-binding activity were indeed observed. The classical pathway was involved in JA-induced inhibition of NF-κB, characterized by decreases in phosphorylation of AKT, IκB kinase (IKK)-β/IKK-α, and IκB-α. Furthermore, JA caused significant translocation of apoptosis-inducing factor and endonuclease G, caspase-independent apoptotic signaling molecules, from the mitochondrial to the nuclei. Our data suggest anti-inflammatory and cytotoxic mechanisms of JA, and using gene expression signatures to identify novel molecular actions of phytochemicals is an effective approach.http://www.sciencedirect.com/science/article/pii/S1756464617302062Justicidin ANF-κBCaspase-independent apoptosisL1000 gene expression profilingConnectivity mapHuman colorectal cancer |
spellingShingle | Shen-Jeu Won Cheng-Hsin Yen Hao-Wen Hsieh Shao-Wei Chang Chun-Nan Lin Chi-Ying F. Huang Chun-Li Su Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor Journal of Functional Foods Justicidin A NF-κB Caspase-independent apoptosis L1000 gene expression profiling Connectivity map Human colorectal cancer |
title | Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor |
title_full | Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor |
title_fullStr | Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor |
title_full_unstemmed | Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor |
title_short | Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor |
title_sort | using connectivity map to identify natural lignan justicidin a as a nf κb suppressor |
topic | Justicidin A NF-κB Caspase-independent apoptosis L1000 gene expression profiling Connectivity map Human colorectal cancer |
url | http://www.sciencedirect.com/science/article/pii/S1756464617302062 |
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