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

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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

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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

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