Quercetin-induced apoptosis prevents EBV infection

Abstract

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.

Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies

“…Quercetin, an aglycone of rutin, is a phytochemical abundant in plants and may diminish the replication of many viruses: highly pathogenic influenza virus [50], rhinovirus [51], dengue virus type-2 [52], HSV-1 [53], poliovirus [54], adenovirus [53], Epstein-Barr virus [55], Mayaro virus [56], Japanese encephalitis virus [57], respiratory syncytial virus [58], and HCV [59,60]. Its antiviral activity mode was studies in a few cases.…”

Prophylactic Efficacy of Quercetin 3-β- O - d -Glucoside against Ebola Virus Infection

“…Quercetin 3-␤-O-D-glucoside (Q3G), for example, is a natural derivative of quercetin that contains a glucoside molecule, and this has been shown to enhance the solubility and bioavailability of the compound when ingested (16). Although much research on quercetin and its derivatives has focused on their properties as potential therapeutic agents against cancer and inflammatory diseases and their anti-metabolic disease effects (17), recent studies have also demonstrated antiviral activity against a wide variety of viruses, including influenza virus, Chikungunya virus, Epstein-Barr virus, hepatitis C virus, and Mayaro virus (18)(19)(20)(21)(22). While a detailed mechanism of action remains undefined, it has been proposed that quercetin and its derivatives affect a step in the viral entry process.…”

Potential Therapeutic Effects of Phytochemicals and Medicinal Herbs for Cancer Prevention and Treatment

“…Other research shows that quercetin inhibits tyrosine kinase, one of the major enzymes associated with cancer and helps flush cancerpromoting chemicals such as BPA (Bisphenol-A) from the body. Importantly, quercetin could be an effective antiviral and antitumor agent against Epstein-Barr Virus (EBV) infection and the human carcinomas it is involved with [3]. Quercetin induces signal transductions to stimulate apoptosis and induces EBV gene transcription; quercetin-induced apoptosis appears to prevent EBV infection.…”

“…Found in red wine, red grapes, and dark berries, resveratrol inhibits cancer by reducing cell proliferation and metastasis and by inducing apoptosis [4]. In particular, resveratrol acts against several genes that promote prostate, colorectal, and other cancers [5].…”