Catalytic inhibition of topoisomerase IIalpha by demethylzeylasterone, a 6-oxophenolic triterpenoid from Kokoona zeylanica

J Nat Prod. 2001 Oct;64(10):1294-6. doi: 10.1021/np010123c.

Abstract

In a study to evaluate celastroloids as potential anticancer agents, demethylzeylasterone (5), a 6-oxophenolic triterpenoid from Kokoona zeylanica, was found to be an inhibitor of the enzyme topoisomerase IIalpha (IC(50) = 17.6 microM). Studies of the relationship of this inhibitor to both DNA and the enzyme resulted in 5 being classified as a "catalytic inhibitor" of topoisomerase II. Demethylzeylasterone selectively inhibits the growth of the breast cancer cell line MCF-7 (IC(50) = 12.5 microM) without inhibiting the growth of non-small cell lung cancer (NCI-H460) and CNS glioma (SF-268) cell lines. This is the first report of topoisomerase II inhibitory activity in a celastroloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Catalysis
  • DNA / antagonists & inhibitors
  • DNA Topoisomerases, Type II
  • DNA-Binding Proteins
  • Electrophoresis, Agar Gel
  • Electrophoretic Mobility Shift Assay
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Glioma
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms
  • Methyl Green
  • Molecular Structure
  • Plants, Medicinal / chemistry*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors*
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification*
  • Triterpenes / pharmacology
  • Tumor Cells, Cultured / drug effects

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Topoisomerase II Inhibitors
  • Triterpenes
  • demethylzeylasterone
  • Methyl Green
  • DNA
  • DNA Topoisomerases, Type II