Erianin induces a JNK/SAPK-dependent metabolic inhibition in human umbilical vein endothelial cells

In Vivo. 2004 Mar-Apr;18(2):223-8.

Abstract

Background: Erianin is a natural product derived from Dendrobium chrysotoxum, with promising antitumor activity.

Materials and methods: To evaluate the metabolic effect of erianin, a cytosensor assay for acidification rate, MTT assay, measurement of lactate, glucose and ATP were performed in human umbilical vein endothelial cells (HUVECs) exposed to 1-100 nM erianin. JNK/SAPK activity was detected by Western blot.

Results: Twelve- or 24- hour incubation with erianin induced a dose-dependent metabolic inhibition, as indicated by reduced acidification rate and cell viability, with an endothelium-selectivity. Erianin caused decreases in lactate production, glucose consumption and intracellular ATP level. Pretreatment with the JNK/SAPK inhibitor SP600125 significantly abolished these inhibitory responses, and especially restored the erianin-induced decreases in ATP and the erianin-induced phosphorylation of JNK/SAPK with dose- and time- dependence.

Conclusion: Erianin inhibited endothelial metabolism in a JNK/SAPK-dependent manner. This mechanism may be involved in the potential antitumnor and antiangiogenic actions of erianin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Angiogenesis Inhibitors / pharmacology*
  • Anthracenes / pharmacology
  • Bibenzyls / pharmacology*
  • Biosensing Techniques
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Formazans / metabolism
  • Glucose / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Lactic Acid / metabolism
  • Mitogen-Activated Protein Kinase 10
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phenol
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism*
  • Tetrazolium Salts / metabolism
  • Umbilical Veins / cytology
  • Umbilical Veins / metabolism

Substances

  • Angiogenesis Inhibitors
  • Anthracenes
  • Bibenzyls
  • Erianin
  • Formazans
  • Tetrazolium Salts
  • pyrazolanthrone
  • MTT formazan
  • Phenol
  • Lactic Acid
  • Adenosine Triphosphate
  • Mitogen-Activated Protein Kinase 10
  • Protein-Tyrosine Kinases
  • Mitogen-Activated Protein Kinases
  • Glucose