title: Prenylated flavonoids and resveratrol derivatives isolated from Artocarpus communis with the ability to overcome TRAIL resistance.
abstract: In a screening program on natural products that can abrogate tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance, four new prenylated flavonoid and resveratrol derivatives (1-4) were isolated from Artocarpus communis, together with eight known prenylflavonoids (5-12). The structures of 1-4 were elucidated spectroscopically. Pannokin D [corrected] (1) (2 μM) and artonin E (5) (3 μM) potently exhibited the ability to overcome TRAIL resistance. Artonin E (5) induced caspase-dependent apoptosis in combination with TRAIL, increased caspase 3/7 activity, and enhanced the protein levels of p53 and DR5. Moreover, this substance decreased cell viability in combination with TRAIL and enhanced the protein levels of DR5, and these effects were mediated by increases in the production of ROS (reactive oxygen species). Thus, artonin E (5) was found to induce extrinsic apoptotic cell death by the ROS- and p53-mediated up-regulation of DR5 expression in AGS cells.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Toume
authors.forename: Tadashi
authors.initials: T
authors.lastname: Habu
authors.forename: Midori A
authors.initials: MA
authors.lastname: Arai
authors.forename: Takashi
authors.initials: T
authors.lastname: Koyano
authors.forename: Thaworn
authors.initials: T
authors.lastname: Kowithayakorn
authors.forename: Masami
authors.initials: M
authors.lastname: Ishibashi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D031622:Artocarpus / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects
chemical_list: D005419:Flavonoids; D017382:Reactive Oxygen Species; D013267:Stilbenes; D053221:TNF-Related Apoptosis-Inducing Ligand; D016159:Tumor Suppressor Protein p53; C000595955:pannokin E; C066727:artonin E; D000077185:Resveratrol