Licochalcone A is a potent inhibitor of TEL-Jak2-mediated transformation through the specific inhibition of Stat3 activation

Megumi Funakoshi-Tago, Kenji Tago, Chiho Nishizawa, Kyoko Takahashi, Tadahiko Mashino, Susumu Iwata, Hideo Inoue, Yoshiko Sonoda, Tadashi Kasahara

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Aberrant activation of Jak/Stat signaling causes a number of hematopoietic disorders and oncogenesis, and therefore the effective inhibitors of the Jak/Stat signaling pathway may be therapeutically useful. TEL-Jak2 gene fusion, which has been identified in human leukemia, encodes a chimeric protein endowed with constitutive tyrosine kinase activity. Expression of TEL-Jak2 protects Ba/F3 cells from IL-3 withdrawal-induced apoptotic cell death and leads to IL-3-independent growth. However, its mechanisms remain to be only partially understood. Here, we first found that Licochalcone A, one of the flavonoids isolated from the root of Glycyrrhiza inflate, inhibited TEL-Jak2-mediated cell proliferation and survival in the absence of IL-3. Licochalcone A failed to inhibit the activity of TEL-Jak2, however, this induced apoptosis of TEL-Jak2-transformed cells with a much lower concentration in the absence of IL-3 than in the presence of IL-3. Interestingly, Licochalcone A significantly inhibited the phosphorylation and nuclear localization of Stat3, which is essential for TEL-Jak2-induced cell transformation. These data suggest that Licochalcone A is a specific inhibitor for Stat3 and would be employed for the treatment of various diseases caused by disorders of the Jak/Stat pathway.

Original languageEnglish
Pages (from-to)1681-1693
Number of pages13
JournalBiochemical Pharmacology
Volume76
Issue number12
DOIs
Publication statusPublished - 2008 Dec 15

Keywords

  • Glycyrrhiza inflate
  • Licochalcone
  • Stat3
  • TEL-Jak2

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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