ent-Sauchinone as Potential Anticancer Agent Inhibiting Migration and Invasion of Human Liver Cancer Cells via Suppressing the STAT3 Signaling Pathway

Chem Biodivers. 2018 Apr;15(4):e1800024. doi: 10.1002/cbdv.201800024. Epub 2018 Apr 16.

Abstract

ent-Sauchinone, a lignan isolated from Saururus chinensis (Lour.) Baill., was reported that it could modulate the expression of signal transducer and activator of transcription 3 (STAT3). Since STAT3 plays a key role in invasion, migration, and metastasis of cancer, we investigated whether ent-sauchinone could exert promising inhibitory effects on the invasion and migration of the metastatic human liver cancer cell line SMMC-7721 in the present study. ent-Sauchinone was extracted from dried herbs of Saururus chinensis (Lour.) Baill. Human liver cancer cell lines SMMC-7721 and HCCLM3 were used to test the effect of ent-sauchinone on cell viability. The IC50 values and time-dependent effect of ent-sauchinone were determined by MTT assay. Cell migration and invasion of SMMC-7721 were evaluated by the wound healing test and transwell assay respectively, the known anti-metastasis agent curcumin was used as a positive control. Western blotting assay was used to investigate relevant molecular mechanisms of cell invasion and migration. Though ent-sauchinone didn't show high cytotoxicity, the wound healing assay and transwell migration assay revealed a profound impairment in the metastatic potential of SMMC-7721 cells due to down-regulation of N-cadherin, MMP-2, and MMP-9 proteins induced by inhibiting the phosphorylation of STAT3. These findings suggest that ent-sauchinone could be used as a promising agent to treat cancer metastasis.

Keywords: STAT3; ent-sauchinone; invasion; migration.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Benzopyrans / chemistry
  • Benzopyrans / isolation & purification
  • Benzopyrans / pharmacology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dioxoles / chemistry
  • Dioxoles / isolation & purification
  • Dioxoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Molecular Structure
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism
  • Saururaceae / chemistry*
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Benzopyrans
  • Dioxoles
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • sauchinone