Cytotoxic activity and molecular targets of atractylodin in cholangiocarcinoma cells

J Pharm Pharmacol. 2019 Feb;71(2):185-195. doi: 10.1111/jphp.13024. Epub 2018 Oct 15.

Abstract

Objectives: To evaluate the cytotoxic activity of atractylodin and its potential effects on heme oxygenase (HO)-1 production, STAT1/3 phosporylation and major NF-κB protein expression in the cholangiocarcinoma-associated cell line CL-6.

Methods: Standard MTT assay was used for accessing antiproliferative activity on CL-6 cells. Normal human embryonic fibroblast (OUMS) cell was taken as control cell line. Colony formation and wound healing assay were conducted to access the effects of atractylodin on cell proliferation and directional migration activity of CL-6 cells. Western blot was used for evaluating levels of protein expression and phosphorylation.

Key findings: Atractylodin exhibited selective cytotoxicity towards CL-6 as compared with OUMS with IC50 of 216.8 (212.4-233.8) and 351.2 (345.7-359.5) μm [median (range)], respectively. Exposure to the compound dose-dependently inhibited colony formation ability and decreased wound closure potential of CL-6 cells. Atractylodin treatment suppressed HO-1 production in CL-6 cells. It dose-dependently inhibited STAT1/3 protein phosphorylation and moderately inhibited NF-κB (p50), NF-κB (p52), and NF-κB (p65) protein expression in both dose- and time-dependent manner.

Conclusions: Atractylodin exerts significant cytotoxic activity against CL-6 cells which may be linked to its suppressive effect on HO-1 production, STAT1/3 phosphorylation and expression of key NF-κB proteins.

Keywords: Atractylodes lancea; CL-6; OUMS; atractylodin; cholangiocarcinoma.

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / pathology
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / pathology
  • Dose-Response Relationship, Drug
  • Furans / administration & dosage
  • Furans / pharmacology*
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Inhibitory Concentration 50
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Time Factors

Substances

  • Antineoplastic Agents, Phytogenic
  • Furans
  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • atractylodin
  • Heme Oxygenase-1