Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor

Shen Jeu Won, Cheng Hsin Yen, Hao Wen Hsieh, Shao Wei Chang, Chun Nan Lin, Chi Ying F. Huang, Chun-Li Su

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)68-76
Number of pages9
JournalJournal of Functional Foods
Volume34
DOIs
Publication statusPublished - 2017 Jul 1

Fingerprint

IKappaB kinase
B-DNA
Lignans
lignans
gene expression
caspases
hepatoma
colorectal neoplasms
phytopharmaceuticals
prostaglandins
Taiwan
phosphorylation
medicine
phosphotransferases (kinases)
apoptosis
cells
China
Transcriptome
Justicia
Apoptosis Inducing Factor

Keywords

  • Caspase-independent apoptosis
  • Connectivity map
  • Human colorectal cancer
  • Justicidin A
  • L1000 gene expression profiling
  • NF-κB

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor. / Won, Shen Jeu; Yen, Cheng Hsin; Hsieh, Hao Wen; Chang, Shao Wei; Lin, Chun Nan; Huang, Chi Ying F.; Su, Chun-Li.

In: Journal of Functional Foods, Vol. 34, 01.07.2017, p. 68-76.

Research output: Contribution to journalArticle

Won, Shen Jeu ; Yen, Cheng Hsin ; Hsieh, Hao Wen ; Chang, Shao Wei ; Lin, Chun Nan ; Huang, Chi Ying F. ; Su, Chun-Li. / Using connectivity map to identify natural lignan justicidin A as a NF-κB suppressor. In: Journal of Functional Foods. 2017 ; Vol. 34. pp. 68-76.
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