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
N1 - Funding Information:
This study was supported by a Grant-in-aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS), Special Funds for Education and Research (Development of SPECT Probes for Pharmaceutical Innovation) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, Iodine Research Project in Chiba University, Asian Core Program (JSPS), the Cosmetology Research Foundation, and Japan Antibiotics Research Association.
PY - 2013
Y1 - 2013
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 - TRAIL
KW - TRAIL-resistance overcoming activity
KW - Thailand
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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 -