Luotonin A. A Naturally Occurring Human DNA Topoisomerase I Poison

Ali Cagir, Shannon H. Jones, Rong Gao, Brian M. Eisenhauer, Sidney M. Hecht

Research output: Contribution to journalArticle

183 Scopus citations

Abstract

Luotonin A is a pyrroloquinazolinoquinoline alkaloid isolated from the Chinese herbal medicinal plant Peganum nigellastrum. Although previously shown to exhibit cytotoxicity against the murine leukemia P-388 cell line, the mechanism of action of luotonin A is unknown. Presently, we demonstrate that luotonin A stabilizes the human DNA topoisomerase I?DNA covalent binary complex, affording the same pattern of cleavage as the structurally related topoisomerase I inhibitor camptothecin. Luotonin A also mediated topoisomerase I-dependent cytotoxicity toward Saccharyomyces cerevisiae lacking yeast topoisomerase I, but harboring a plasmid having the human topoisomerase I gene under the control of a galactose promoter. This finding identifies a putative biochemical locus for the cytotoxic action of luotonin A and has important implications for the mechanism of action of camptothecin and the design of camptothecin analogues.

Original languageEnglish (US)
Pages (from-to)13628-13629
Number of pages2
JournalJournal of the American Chemical Society
Volume125
Issue number45
DOIs
StatePublished - Nov 12 2003

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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