Inhibitors of the NF-kappaB activation pathway from Cryptocarya rugulosa.
The nuclear factor-kappaB (NF-kappaB) signaling pathway is constitutively active in many types of cancers and is a potential therapeutic target. Using a cell-based assay for stability of inhibitor of kappa B (IkappaB), a critical regulator of NF-kappaB activity, we found that an organic solvent extract of the plant Cryptocarya rugulosa inhibited constitutive NF-kappaB activity in human lymphoma cell lines. The active components were identified as rugulactone, a new alpha-pyrone (1), and the known cryptocaryone (2). Rugulactone was the more active compound, exhibiting up to 5-fold induction of IkappaB at 25 microg/mL; maximal activity was observed with 10 h exposure of test cells to 1 or 2.
Meragelman
Tamara L
TL
Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, Maryland, USA.
Scudiero
Dominic A
DA
Davis
R Eric
RE
Staudt
Louis M
LM
McCloud
Thomas G
TG
Cardellina
John H
JH
Shoemaker
Robert H
RH
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D031369:Cryptocarya / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008296:Malaysia; D015394:Molecular Structure; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D016328:NF-kappa B; D011753:Pyrones; C548572:cryptocaryone; C548571:rugulactone; D051550:I-kappa B Kinase