Quercetin-induced apoptosis prevents EBV infection
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Minjung Lee1, Myoungki Son1, Eunhyun Ryu1, Yu Su Shin2, Jong Gwang Kim3, Byung Woog Kang3, Gi-Ho Sung4, Hyosun Cho5 and Hyojeung Kang1
1 College of Pharmacy and Institute of Microorganisms, Kyungpook National University, Daegu, Republic of Korea
2 Department of Medicinal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, Republic of Korea
3 Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea
4 Institute for Bio-Medical Convergence, International St. Mary’s Hospital, College of Medicine, Catholic Kwangdong University, Incheon, Republic of Korea
5 College of Pharmacy and Innovative Drug Center, Duksung Women’s University, Seoul, Republic of Korea
Hyojeung Kang, email:
Hyosun Cho, email:
Keywords: quercetin, isoliquiritigenin, Epstein-Barr virus, gastric carcinoma, apoptosis
Received: December 03, 2014 Accepted: March 03, 2015 Published: March 29, 2015
Epstein-Barr virus (EBV) is a human gamma-1 herpesvirus that establishes a lifelong latency in over 90% of the world’s population. During latency, virus exists predominantly as a chromatin-associated, multicopy episome in the nuclei of a variety of tumor cells derived from B cells, T cells, natural killer (NK) cells, and epithelial cells. Licorice is the root of Glycyrrhiza uralensis or G. glabra that has traditionally cultivated in eastern part of Asia. Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth. Quercetin and isoliquiritigenin are produced from licorice and highly similar in molecular structure. They have diverse bioactive effects such as antiviral activity, anti-asthmatic activity, anti-cancer activity, anti-inflammation activity, monoamine-oxidase inhibitor, and etc. To determine anti-EBV and anti-EBVaGC (Epstein-Barr virus associated gastric carcinoma) effects of licorice, we investigated antitumor and antiviral effects of quercetin and isoliquiritigenin against EBVaGC. Although both quercetin and isoliquiritigenin are cytotoxic to SNU719 cells, quercetin induced more apoptosis in SNU719 cells than isoliquiritigenin, more completely eliminated DNMT1 and DNMT3A expressions than isoliquiritigenin, and more strongly affects the cell cycle progression of SNU719 than isoliquiritigenin. Both quercetin and isoliquiritigenin induce signal transductions to stimulate apoptosis, and induce EBV gene transcription. Quercetin enhances frequency of F promoter use, whereas isoliquiritigenin enhances frequency of Q promoter use. Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency. Quercetin increases more the EBV progeny production, and inhibits more EBV infection than isoliquiritigenin. These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma.
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