Iciartin, a novel FASN inhibitor, exerts anti-melanoma activities through IGF-1R/STAT3 signaling

Jinfeng Wu, Juan Du, Xiuqiong FU, Bin Liu, Huihui Cao, Ting Li, Tao Su, Jinhua Xu, Anfernee K W TSE*, Zhiling YU

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Icaritin (IT) is a flavonoid isolated from Herba Epimedii. In this study, we evaluated the anti-melanoma activities of IT, and determined its cytotoxic mechanism. We found that IT exerted cytotoxicity to melanoma cells. Furthermore, IT induced melanoma cell apoptosis, which was accompanied with PARP cleavage. Mechanistically, IT suppressed p-STAT3 (tyr705) level in parallel with increases of p-STAT3 (ser727), p-ERK and p-AKT. IT significantly inhibited STAT3 nuclear translocation and reduced the levels of STAT3 -targeted genes. IT also inhibited IGF-1-induced STAT3 activation through down-regulation of total IGF-1R level. No dramatic changes in IGF-1R mRNA levels were observed in IT-treated cells, suggesting that IT acted primarily at a posttranscriptional level. Using molecular docking analysis, IT was identified as a novel fatty acid synthase (FASN) inhibitor. We found that IT reduced the level of total IGF-1R via FASN inhibition. In summary, we reported that IT exerted anti-melanoma activities, and these effects were partially due to inhibition of FASN/IGF-1R/STAT3 signaling.

Original languageEnglish
Pages (from-to)51251-51269
Number of pages19
JournalOncotarget
Volume7
Issue number32
DOIs
Publication statusPublished - 1 Aug 2016

Scopus Subject Areas

  • Oncology

User-Defined Keywords

  • FASN
  • Icartin
  • IGF-1R
  • Melanoma
  • STAT3

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