Prenylflavonoids isolated from Artocarpus champeden with TRAIL-resistance overcoming activity.
In a screening program for bioactive natural products which can overcome Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-resistance, three prenylflavonoids, named pannokin A-C, were isolated from a MeOH extract of Artocarpus champeden (Moraceae) roots, together with three known prenylflavonoids. The structures of pannokin A-C were elucidated by spectroscopic analysis. These of the prenylflavonoids in combination with TRAIL, showed cytotoxic activity in sensitizing TRAIL-resistant human gastric adenocarcinoma (AGS) cells. Of these compounds, heterophyllin increased caspase 3/7 activity when combined with TRAIL in AGS cells, and enhanced the expression of DR4 and DR5 mRNA. Moreover, heterophyllin up-regulated mRNA expression of CCAAT/enhancer-binding protein-homologous protein (CHOP) which was reported to be an important regulator of DR5 expression. Thus, heterophyllin was presumed to cause a CHOP-dependent up-regulation of DR5 expression resulting in apoptosis in AGS cells.
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Tomohiro
T
Minakawa
Kazufumi
K
Toume
Midori A
MA
Arai
Takashi
T
Koyano
Thaworn
T
Kowithayakorn
Masami
M
Ishibashi
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D031622:Artocarpus / Q000737:chemistry*; D001483:Base Sequence; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D018517:Plant Roots / Q000737:chemistry; D012333:RNA, Messenger / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D013785:Thailand; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D005419:Flavonoids; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C000589063:pannokin A; C000589065:pannokin B; C000589067:pannokin C
Artocarpus champeden; Prenylflavonoids; TRAIL; TRAIL-resistance overcoming activity; Thailand