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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Main Authors: Shen-Jeu Won, Cheng-Hsin Yen, Hao-Wen Hsieh, Shao-Wei Chang, Chun-Nan Lin, Chi-Ying F. Huang, Chun-Li Su
Format: Article
Language:English
Published: Elsevier 2017-07-01
Series:Journal of Functional Foods
Subjects:
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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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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