Prenylflavonoids isolated from Artocarpus champeden with TRAIL-resistance overcoming activity

Tomohiro Minakawa; Kazufumi Toume; Midori A. Arai; Takashi Koyano; Thaworn Kowithayakorn; Masami Ishibashi

doi:10.1016/j.phytochem.2013.08.015

Prenylflavonoids isolated from Artocarpus champeden with TRAIL-resistance overcoming activity

Tomohiro Minakawa, Kazufumi Toume, Midori A. Arai, Takashi Koyano, Thaworn Kowithayakorn, Masami Ishibashi^*

^*Corresponding author for this work

Department of Medicinal Resources Management, Institute of Natural Medicine

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	299-304
Number of pages	6
Journal	Phytochemistry
Volume	96
DOIs	https://doi.org/10.1016/j.phytochem.2013.08.015
State	Published - 2013

Keywords

Artocarpus champeden
Prenylflavonoids
TRAIL
TRAIL-resistance overcoming activity
Thailand

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Plant Science
Horticulture

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10.1016/j.phytochem.2013.08.015

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@article{ab3192a30de043e1b27f35d9c23dbfd0,

title = "Prenylflavonoids isolated from Artocarpus champeden with TRAIL-resistance overcoming activity",

abstract = "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.",

keywords = "Artocarpus champeden, Prenylflavonoids, TRAIL, TRAIL-resistance overcoming activity, Thailand",

author = "Tomohiro Minakawa and Kazufumi Toume and Arai, {Midori A.} and Takashi Koyano and Thaworn Kowithayakorn and Masami Ishibashi",

note = "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.",

year = "2013",

doi = "10.1016/j.phytochem.2013.08.015",

language = "英語",

volume = "96",

pages = "299--304",

journal = "Phytochemistry",

issn = "0031-9422",

publisher = "Elsevier Ltd.",

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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

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SN - 0031-9422

VL - 96

SP - 299

EP - 304

JO - Phytochemistry

JF - Phytochemistry

ER -

Prenylflavonoids isolated from Artocarpus champeden with TRAIL-resistance overcoming activity

Abstract

Keywords

ASJC Scopus subject areas

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