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
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Neoplasm
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / isolation & purification*
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Antineoplastic Agents / pharmacology
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Breast Neoplasms
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Carcinoma, Non-Small-Cell Lung
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Catalysis
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DNA / antagonists & inhibitors
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DNA Topoisomerases, Type II
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DNA-Binding Proteins
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Electrophoresis, Agar Gel
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Electrophoretic Mobility Shift Assay
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification*
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Enzyme Inhibitors / pharmacology
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Female
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Glioma
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Humans
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Inhibitory Concentration 50
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Lung Neoplasms
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Methyl Green
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Molecular Structure
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Plants, Medicinal / chemistry*
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / metabolism
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Structure-Activity Relationship
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Topoisomerase II Inhibitors*
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Triterpenes / chemistry
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Triterpenes / isolation & purification*
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Triterpenes / pharmacology
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Tumor Cells, Cultured / drug effects
Substances
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Antigens, Neoplasm
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Antineoplastic Agents
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DNA-Binding Proteins
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Enzyme Inhibitors
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Topoisomerase II Inhibitors
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Triterpenes
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demethylzeylasterone
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Methyl Green
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DNA
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DNA Topoisomerases, Type II