Guttiferone K suppresses cell motility and metastasis of hepatocellular carcinoma by restoring aberrantly reduced profilin 1

Kaikai Shen, Zhichao Xi, Jianling Xie, Hua Wang, Chanlu Xie, C. Soon Lee, Paul Fahey, Qihan Dong, Hongxi Xu

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy and the 5-year survival rate of advanced HCC is < 10%. Guttiferone K (GUTK) isolated from the Garcinia genus inhibited HCC cells migration and invasion in vitro and metastasis in vivo without apparent toxicity. Proteomic analysis revealed that actin-binding protein profilin 1 (PFN1) was markedly increased in the presence of GUTK. Over-expression of PFN1 mimicked the effect of GUTK on HCC cell motility and metastasis. The effect of GUTK on cell motility was diminished when PFN1 was over-expressed or silenced. Over-expression of PFN1 or incubation with GUTK decreased F-actin levels and the expression of proteins involved in actin nucleation, branching and polymerization. Moreover, a reduction of PFN1 protein levels was common in advanced human HCC and associated with poor survival rate. In conclusion, GUTK effectively suppresses the motility and metastasis of HCC cells mainly by restoration of aberrantly reduced PFN1 protein expression.

Original languageEnglish
Pages (from-to)56650-56663
Number of pages14
JournalOncotarget
Volume7
Issue number35
DOIs
Publication statusPublished or Issued - 2016

Keywords

  • Actin
  • Cancer metastasis
  • Guttiferone K
  • Hepatocellular carcinoma
  • Profilin1

ASJC Scopus subject areas

  • Oncology

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