TY - JOUR
T1 - Prenylflavonoids isolated from Artocarpus champeden with TRAIL-resistance overcoming activity
AU - Minakawa, Tomohiro
AU - Toume, Kazufumi
AU - Arai, Midori A.
AU - Koyano, Takashi
AU - Kowithayakorn, Thaworn
AU - Ishibashi, Masami
PY - 2013/9/25
Y1 - 2013/9/25
N2 - 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.
AB - 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.
KW - Artocarpus champeden
KW - Prenylflavonoids
KW - Thailand
KW - TRAIL
KW - TRAIL-resistance overcoming activity
UR - http://www.scopus.com/inward/record.url?scp=84888329095&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888329095&partnerID=8YFLogxK
U2 - 10.1016/j.phytochem.2013.08.015
DO - 10.1016/j.phytochem.2013.08.015
M3 - Article
C2 - 24074554
AN - SCOPUS:84888329095
VL - 96
SP - 299
EP - 304
JO - Phytochemistry
JF - Phytochemistry
SN - 0031-9422
ER -