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Journal of Natural Products 2015-Jan

Prenylated flavonoids and resveratrol derivatives isolated from Artocarpus communis with the ability to overcome TRAIL resistance.

Watumiaji waliosajiliwa tu ndio wanaweza kutafsiri nakala
Ingia / Ingia
Kiungo kimehifadhiwa kwenye clipboard
Kazufumi Toume
Tadashi Habu
Midori A Arai
Takashi Koyano
Thaworn Kowithayakorn
Masami Ishibashi

Maneno muhimu

Kikemikali

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.

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