title: Inhibitors of the NF-kappaB activation pathway from Cryptocarya rugulosa.
abstract: 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.
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, Maryland, USA.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Meragelman
authors.forename: Dominic A
authors.initials: DA
authors.lastname: Scudiero
authors.forename: R Eric
authors.initials: RE
authors.lastname: Davis
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Thomas G
authors.initials: TG
authors.lastname: McCloud
authors.forename: John H
authors.initials: JH
authors.lastname: Cardellina
authors.forename: Robert H
authors.initials: RH
authors.lastname: Shoemaker
mesh_terms: 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*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D016328:NF-kappa B; D011753:Pyrones; C548572:cryptocaryone; C548571:rugulactone; D051550:I-kappa B Kinase