Prenylflavonoids isolated from Artocarpus champeden with TRAIL-resistance overcoming activity

被引：11

作者：

Minakawa, Tomohiro ^{[1
]}

Toume, Kazufumi ^{[1
]}

Arai, Midori A. ^{[1
]}

Koyano, Takashi ^{[2
]}

Kowithayakorn, Thaworn ^{[3
]}

Ishibashi, Masami ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Pharmaceut Sci, Chuo Ku, Chiba 2608675, Japan

[2] Temko Corp, Nakano Ku, Tokyo 1640012, Japan

[3] Khon Kaen Univ, Fac Agr, Khon Kaen 40002, Thailand

来源：

PHYTOCHEMISTRY | 2013年 / 96卷

基金：

日本学术振兴会;

关键词：

TRAIL; Prenylflavonoids; Artocarpus champeden; TRAIL-resistance overcoming activity; Thailand; DEATH RECEPTOR 5; SCREENING-PROGRAM; CANCER CELLS; INDUCED APOPTOSIS; UP-REGULATION; HETEROPHYLLUS; CYTOTOXICITY; ENHANCEMENT; COMBINATION; EXPRESSION;

D O I：

10.1016/j.phytochem.2013.08.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：299 / 304

页数：6

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