Novel heparan sulfate mimetic compounds as antitumor agents

Chem Biol. 2004 Mar;11(3):367-77. doi: 10.1016/j.chembiol.2004.02.015.

Abstract

Heparan sulfate glycosaminoglycans (HSGAGs) are involved in tumor cell growth, adhesion, invasion, and migration, due to their interactions with various proteins. In this study, novel HSGAG-mimetic compounds (KI compounds) were designed and synthesized. As a result of cell-based assays, KI-105 was found to exert potent inhibitory activities against migration and invasion of human fibrosarcoma HT1080 cells. The present results indicate that a novel invasion/migration inhibitor, KI-105, can increase the adherence of HT1080 cells. It was conceivable that this cellular effect was caused by an increase in the amount of cell-surface HSGAGs and focal adhesions. Although further investigations are needed to decipher the molecular mechanism of KI-105, it is suggested that heparanase and Cdc42 are involved in its biological effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Drug Design*
  • Glucuronidase / antagonists & inhibitors
  • Glucuronidase / metabolism
  • Heparitin Sulfate / chemistry*
  • Heparitin Sulfate / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Phenotype
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Heparitin Sulfate
  • heparanase
  • Glucuronidase