Quassinoid inhibition of AP-1 function does not correlate with cytotoxicity or protein synthesis inhibition.
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.
Beutler
John A
JA
Molecular Targets Development Program and Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA. beutlerj@mail.nih.gov
Kang
Moon-Il
MI
Robert
Francis
F
Clement
Jason A
JA
Pelletier
Jerry
J
Colburn
Nancy H
NH
McKee
Tawnya C
TC
Goncharova
Ekaterina
E
McMahon
James B
JB
Henrich
Curtis J
CJ
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*
D003603:Cytotoxins; D011500:Protein Synthesis Inhibitors; D036702:Quassins; D018808:Transcription Factor AP-1; C548791:ailanthinone; C015235:glaucarubinone; D005900:Glaucarubin