Investigation of the biological mode of action of clerocidin using whole cell assays

Bioorg Med Chem. 2001 Jun;9(6):1365-70. doi: 10.1016/s0968-0896(01)00051-7.

Abstract

Clerocidin, a diterpenoid natural product, has been shown in vitro to inhibit DNA religation following cleavage by topoisomerase II. Herein, we characterize the efficacy and specificity of clerocidin in HeLa cells. Our results suggest that clerocidin recognizes topoisomerase II as its main intracellular target and binds to this enzyme prior to formation of the 'cleavable complex' with DNA. These pharmacological features attest to the promising chemotherapeutic potential of this natural product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • DNA Topoisomerases, Type II / drug effects*
  • DNA Topoisomerases, Type II / metabolism
  • Diterpenes / pharmacology*
  • HeLa Cells / drug effects
  • HeLa Cells / virology
  • Humans
  • Membrane Glycoproteins*
  • Protein Biosynthesis
  • Protein Transport / drug effects
  • Transcription, Genetic
  • Viral Envelope Proteins / drug effects
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism

Substances

  • Anti-Bacterial Agents
  • Diterpenes
  • G protein, vesicular stomatitis virus
  • Membrane Glycoproteins
  • Viral Envelope Proteins
  • clerocidin
  • DNA Topoisomerases, Type II