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

Kazufumi Toume, Tadashi Habu, Midori A. Arai, Takashi Koyano, Thaworn Kowithayakorn, Masami Ishibashi

研究成果: Article

14 引用 (Scopus)

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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 E (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.

元の言語English
ページ(範囲)103-110
ページ数8
ジャーナルJournal of Natural Products
78
発行部数1
DOI
出版物ステータスPublished - 2015 1 23
外部発表Yes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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