Modulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia

Christopher M. Sturgeon, Kyle Craig, Colleen Brown, Natalie T. Rundle, Raymond J. Andersen, Michel Roberge

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

A phenotypic cell-based assay for inhibitors of the G2 DNA damage checkpoint was used to screen plant extracts from the US National Cancer Institute Natural Products Repository. It revealed activity in a methanol extract from the common ragweed Ambrosia artemisiifolia. Assay-guided fractionation led to the identification of the sesquiterpene lactones psilostachyins A and C as novel checkpoint inhibitors. Elimination of their α,β-unsaturated carbonyl group caused a loss of activity, suggesting that the compounds can bind covalently to target proteins through Michael addition. Psilostachyins A and C also blocked cells in mitosis and caused the formation of aberrant microtubule spindles. However, the compounds did not interfere with microtubule polymerization in vitro. The related sesquiterpene lactones psilostachyin B, paulitin and isopaulitin were also isolated from the same extract but showed no checkpoint inhibition. The identification of the target(s) of psilostachyins A and C may provide further insight into the signalling pathways involved in cell cycle arrest and mitotic progression.

Original languageEnglish
Pages (from-to)938-943
Number of pages6
JournalPlanta Medica
Volume71
Issue number10
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Keywords

  • Ambrosia artemisiifolia
  • Cancer
  • Cell cycle
  • Checkpoint
  • G phase
  • Mitosis

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