Silibinin inhibits the invasion of IL-6-stimulated colon cancer cells via selective JNK/AP-1/MMP-2 modulation in vitro

Chiu Mei Lin, Yen Hsu Chen, Hon Ping Ma, Bao Wei Wang, Jen Hwey Chiu, Su Kiat Chua, Jiann Ruey Ong, Kou-Gi Shyu

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Silibinin is a flavonoid with antihepatotoxic properties and pleiotropic anticancer capabilities. This study investigated silibinin inhibition of cell invasion by down-regulating matrix metalloproteinase-2 (MMP-2) expression, via attenuation of activator protein-1 (AP-1) in IL-6-stimulated LoVo colon cancer cells. Western blot data showed that the expression of MMP-2 protein was reduced 1.6-or 1.7-fold over the control by treatment with silibinin or JNK inhibitor in the models. Similar results were revealed in zymography and confocal microscopy. Pretreatment with silibinin also abolished the binding activity of AP-1 and MMP-2 promoter activity via AP-1 binding, as observed by EMSA and luciferase assay. Finally, a [3H]-thymidine incorporation proliferation assay and cell migration assay demonstrated that silibinin inhibited IL-6-stimulated LoVo cell proliferation and invasion. Taken together, these data indicated that silibinin inhibits LoVo cell invasion with the reduction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel antimetastatic application for silibinin in colon cancer chemoprevention.

Original languageEnglish
Pages (from-to)12451-12457
Number of pages7
JournalJournal of Agricultural and Food Chemistry
Volume60
Issue number51
DOIs
Publication statusPublished - Dec 26 2012

Keywords

  • AP-1
  • colon cancer
  • IL-6
  • MMP-2
  • silibinin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

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