Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma

Licorice extracts have been widely used in herbal and folk medications. Glycyrrhiza contains diverse range of biological compounds including triterpenes (glycyrrhizin, glycyrrhizic acid) and flavonoids (quercetin, liquiritin, liquiritigenin, glabridin, licoricidin, isoliquiritigenin). The flavonoids...

Full description

Bibliographic Details
Main Authors: Hwan Hee Lee, Seulki Lee, Yu Su Shin, Miyeon Cho, Hyojeung Kang, Hyosun Cho
Format: Article
Language:English
Published: MDPI AG 2016-09-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/21/10/1286
_version_ 1818479515080327168
author Hwan Hee Lee
Seulki Lee
Yu Su Shin
Miyeon Cho
Hyojeung Kang
Hyosun Cho
author_facet Hwan Hee Lee
Seulki Lee
Yu Su Shin
Miyeon Cho
Hyojeung Kang
Hyosun Cho
author_sort Hwan Hee Lee
collection DOAJ
description Licorice extracts have been widely used in herbal and folk medications. Glycyrrhiza contains diverse range of biological compounds including triterpenes (glycyrrhizin, glycyrrhizic acid) and flavonoids (quercetin, liquiritin, liquiritigenin, glabridin, licoricidin, isoliquiritigenin). The flavonoids in licorice are known to have strong anti-cancer activities. Quercetin, the most abundant flavonoid, has been shown to have anti-ulcer, anti-cancer, antioxidant, and anti-inflammatory properties. Latent Epstein-Barr virus (EBV) infection can lead to serious malignancies, such as, Burkitt’s lymphoma, Hodgkin’s disease and gastric carcinoma(GC), and (Epstein-Barr virus associated gastric carcinoma) EBVaGC is one of the most common EBV-associated cancers. In this study, the authors first examined the anti-cancer effects of quercetin and isoliquiritigenin in vivo xenograft animal models implanted with EBV(+) human gastric carcinoma (SNU719) or EBV(−) human gastric carcinoma (MKN74), and then explored the molecular mechanisms responsible for their anti-cancer activities. The results obtained showed that anti-cancer effect of quercetin was greater than isoliquiritigenin in mice injected with EBV(+) human gastric carcinoma (SNU719) cells. On the other hand, quercetin and isoliquiritigenin had similar anti-cancer effects in mice injected with EBV(−) human gastric carcinoma (MKN74) cells. Interestingly, quercetin inhibited EBV viral protein expressions, including EBNA-1 and LMP-2 proteins in tumor tissues from mice injected with EBV(+) human gastric carcinoma. Quercetin more effectively induced p53-dependent apoptosis than isoliquiritigenin in EBV(+) human gastric carcinoma, and this induction was correlated with increased expressions of the cleaved forms of caspase-3, -9, and Parp. In EBV(−)human gastric carcinoma (MKN74), both quercetin and isoliquiritigenin induced the expressions of p53, Bax, and Puma and the cleaved forms of caspase-3 and -9 and Parp at similar levels.
first_indexed 2024-12-10T11:11:41Z
format Article
id doaj.art-c72aee84a9994e03900931aad2695420
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-12-10T11:11:41Z
publishDate 2016-09-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-c72aee84a9994e03900931aad26954202022-12-22T01:51:23ZengMDPI AGMolecules1420-30492016-09-012110128610.3390/molecules21101286molecules21101286Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric CarcinomaHwan Hee Lee0Seulki Lee1Yu Su Shin2Miyeon Cho3Hyojeung Kang4Hyosun Cho5College of Pharmacy, Duksung Women’s University, Seoul 132-714, KoreaCollege of Pharmacy, Duksung Women’s University, Seoul 132-714, KoreaDepartment of Medicinal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 369-873, KoreaCollege of Pharmacy, Research Institute of Pharmaceutical Sciences and Institute for Microorganisms, Kyungpook National University, Daegu 702-701, KoreaCollege of Pharmacy, Research Institute of Pharmaceutical Sciences and Institute for Microorganisms, Kyungpook National University, Daegu 702-701, KoreaCollege of Pharmacy, Duksung Women’s University, Seoul 132-714, KoreaLicorice extracts have been widely used in herbal and folk medications. Glycyrrhiza contains diverse range of biological compounds including triterpenes (glycyrrhizin, glycyrrhizic acid) and flavonoids (quercetin, liquiritin, liquiritigenin, glabridin, licoricidin, isoliquiritigenin). The flavonoids in licorice are known to have strong anti-cancer activities. Quercetin, the most abundant flavonoid, has been shown to have anti-ulcer, anti-cancer, antioxidant, and anti-inflammatory properties. Latent Epstein-Barr virus (EBV) infection can lead to serious malignancies, such as, Burkitt’s lymphoma, Hodgkin’s disease and gastric carcinoma(GC), and (Epstein-Barr virus associated gastric carcinoma) EBVaGC is one of the most common EBV-associated cancers. In this study, the authors first examined the anti-cancer effects of quercetin and isoliquiritigenin in vivo xenograft animal models implanted with EBV(+) human gastric carcinoma (SNU719) or EBV(−) human gastric carcinoma (MKN74), and then explored the molecular mechanisms responsible for their anti-cancer activities. The results obtained showed that anti-cancer effect of quercetin was greater than isoliquiritigenin in mice injected with EBV(+) human gastric carcinoma (SNU719) cells. On the other hand, quercetin and isoliquiritigenin had similar anti-cancer effects in mice injected with EBV(−) human gastric carcinoma (MKN74) cells. Interestingly, quercetin inhibited EBV viral protein expressions, including EBNA-1 and LMP-2 proteins in tumor tissues from mice injected with EBV(+) human gastric carcinoma. Quercetin more effectively induced p53-dependent apoptosis than isoliquiritigenin in EBV(+) human gastric carcinoma, and this induction was correlated with increased expressions of the cleaved forms of caspase-3, -9, and Parp. In EBV(−)human gastric carcinoma (MKN74), both quercetin and isoliquiritigenin induced the expressions of p53, Bax, and Puma and the cleaved forms of caspase-3 and -9 and Parp at similar levels.http://www.mdpi.com/1420-3049/21/10/1286EBVhuman gastric carcinomap53quercetinSNU719
spellingShingle Hwan Hee Lee
Seulki Lee
Yu Su Shin
Miyeon Cho
Hyojeung Kang
Hyosun Cho
Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma
Molecules
EBV
human gastric carcinoma
p53
quercetin
SNU719
title Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma
title_full Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma
title_fullStr Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma
title_full_unstemmed Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma
title_short Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma
title_sort anti cancer effect of quercetin in xenograft models with ebv associated human gastric carcinoma
topic EBV
human gastric carcinoma
p53
quercetin
SNU719
url http://www.mdpi.com/1420-3049/21/10/1286
work_keys_str_mv AT hwanheelee anticancereffectofquercetininxenograftmodelswithebvassociatedhumangastriccarcinoma
AT seulkilee anticancereffectofquercetininxenograftmodelswithebvassociatedhumangastriccarcinoma
AT yusushin anticancereffectofquercetininxenograftmodelswithebvassociatedhumangastriccarcinoma
AT miyeoncho anticancereffectofquercetininxenograftmodelswithebvassociatedhumangastriccarcinoma
AT hyojeungkang anticancereffectofquercetininxenograftmodelswithebvassociatedhumangastriccarcinoma
AT hyosuncho anticancereffectofquercetininxenograftmodelswithebvassociatedhumangastriccarcinoma