title: Quassinoid inhibition of AP-1 function does not correlate with cytotoxicity or protein synthesis inhibition.
abstract: Several quassinoids were identified in a high-throughput screening assay as inhibitors of the transcription factor AP-1. Further biological characterization revealed that while their effect was not specific to AP-1, protein synthesis inhibition and cell growth assays were inconsistent with a mechanism of simple protein synthesis inhibition. Numerous plant extracts from the plant family Simaroubaceae were also identified in the same screen; bioassay-guided fractionation of one extract (Ailanthus triphylla) yielded two known quassinoids, ailanthinone (3) and glaucarubinone (4), which were also identified in the pure compound screening procedure.
authors.affiliation: Molecular Targets Development Program and Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA. beutlerj@mail.nih.gov
authors.forename: John A
authors.initials: JA
authors.lastname: Beutler
authors.forename: Moon-Il
authors.initials: MI
authors.lastname: Kang
authors.forename: Francis
authors.initials: F
authors.lastname: Robert
authors.forename: Jason A
authors.initials: JA
authors.lastname: Clement
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Colburn
authors.forename: Tawnya C
authors.initials: TC
authors.lastname: McKee
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Goncharova
authors.forename: James B
authors.initials: JB
authors.lastname: McMahon
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Henrich
mesh_terms: D032268:Ailanthus / Q000737:chemistry*; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005900:Glaucarubin / Q000031:analogs & derivatives; D006801:Humans; D015394:Molecular Structure; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D036702:Quassins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*
chemical_list: D003603:Cytotoxins; D011500:Protein Synthesis Inhibitors; D036702:Quassins; D018808:Transcription Factor AP-1; C548791:ailanthinone; C015235:glaucarubinone; D005900:Glaucarubin