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Quercetin-induced apoptosis prevents EBV infection.

Lee M, Son M, Ryu E, Shin YS, Kim JG, Kang BW, Cho H, Kang H - Oncotarget (2015)

Bottom Line: Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth.Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency.These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and Institute of Microorganisms, Kyungpook National University, Daegu, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of quercetin or isoliquiritigenin on EBV protein productionEBV Protein levels were assessed by Western blot assay using anti-EBV EBNA1, BZLF1 and LMP2A antibodies to define if treatments of quercetin or isoliquiritigenin affect EBV translation in SNU719 or AGS cells. (A) The effects of treatments of quercetin or isoliquritigenin on EBV protein expression in SNU719 cells. Treatments were conducted for 48 h. GAPDH was used as an internal control in the western blot analysis. ISL and QST stands for isoliquiritigenin (62 μM) and quercetin (45 μM), respectively. (B) Time kinetics of effects of quercetin and isoliquritigenin on EBV protein production in SNU719 cells. Treatments were conducted for 0 h, 24 h and 48 h. D, Q, I and T/N stands for treatments of DMSO, quercetin (45 μM), isoliquritigenin (62 μM) and TPA (20 ng/mL) /NaB (3 mM), respectively. (C, D, E) The effect of EBV infection on the expression of EBV protein expression in EBV-negative AGS cells (C), wild type (wt) EBV infected AGS cells (D), and recombinant EBV infected AGS cells (E) [41]. DMSO, QST62, ISL45, and TPA/NaB stand for DMSO treatment, 62 μM isoliquiritigenin treatment, 45 μM quercetin treatment, and TPA (20 ng/mL) and NaB (3 mM) co-treatment, respectively.
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Figure 7: Effects of quercetin or isoliquiritigenin on EBV protein productionEBV Protein levels were assessed by Western blot assay using anti-EBV EBNA1, BZLF1 and LMP2A antibodies to define if treatments of quercetin or isoliquiritigenin affect EBV translation in SNU719 or AGS cells. (A) The effects of treatments of quercetin or isoliquritigenin on EBV protein expression in SNU719 cells. Treatments were conducted for 48 h. GAPDH was used as an internal control in the western blot analysis. ISL and QST stands for isoliquiritigenin (62 μM) and quercetin (45 μM), respectively. (B) Time kinetics of effects of quercetin and isoliquritigenin on EBV protein production in SNU719 cells. Treatments were conducted for 0 h, 24 h and 48 h. D, Q, I and T/N stands for treatments of DMSO, quercetin (45 μM), isoliquritigenin (62 μM) and TPA (20 ng/mL) /NaB (3 mM), respectively. (C, D, E) The effect of EBV infection on the expression of EBV protein expression in EBV-negative AGS cells (C), wild type (wt) EBV infected AGS cells (D), and recombinant EBV infected AGS cells (E) [41]. DMSO, QST62, ISL45, and TPA/NaB stand for DMSO treatment, 62 μM isoliquiritigenin treatment, 45 μM quercetin treatment, and TPA (20 ng/mL) and NaB (3 mM) co-treatment, respectively.

Mentions: Similar to the transcription assay, we were interested in whether the expression of EBV protein was also affected by quercetin or isoliquiritigenin treatments. To analyze EBV protein expression, Western blot assay using anti-EBV EBNA1, BZLF1, and LMP2A antibodies was conducted with SNU719 treated either quercetin or isoliquiritigenin for 48 h. Like transcription patterns of EBV genes affected by both compounds, the Western assay showed that quercetin did enhance BZLF1 and LMP2A expressions, however, isoliquiritigenin remarkably induced LMP2A expressions (Figure 7A). In addition, in order to define time kinetics of effects of quercetin and isoliquritigenin on EBV protein production, the effects by the two compounds were determined on time course of SNU719 treated with quercetin or isoliquritigenin. During 48 h time course, quercetin treatment enhanced BZLF1 expression, yet suppressed EBNA1 expression. In contrast, isoliquiritigenin treatment exhibited little effect on BZLF1 expression and EBNA1 expression during the time course except 24 h post treatment (Figure 7B).


Quercetin-induced apoptosis prevents EBV infection.

Lee M, Son M, Ryu E, Shin YS, Kim JG, Kang BW, Cho H, Kang H - Oncotarget (2015)

Effects of quercetin or isoliquiritigenin on EBV protein productionEBV Protein levels were assessed by Western blot assay using anti-EBV EBNA1, BZLF1 and LMP2A antibodies to define if treatments of quercetin or isoliquiritigenin affect EBV translation in SNU719 or AGS cells. (A) The effects of treatments of quercetin or isoliquritigenin on EBV protein expression in SNU719 cells. Treatments were conducted for 48 h. GAPDH was used as an internal control in the western blot analysis. ISL and QST stands for isoliquiritigenin (62 μM) and quercetin (45 μM), respectively. (B) Time kinetics of effects of quercetin and isoliquritigenin on EBV protein production in SNU719 cells. Treatments were conducted for 0 h, 24 h and 48 h. D, Q, I and T/N stands for treatments of DMSO, quercetin (45 μM), isoliquritigenin (62 μM) and TPA (20 ng/mL) /NaB (3 mM), respectively. (C, D, E) The effect of EBV infection on the expression of EBV protein expression in EBV-negative AGS cells (C), wild type (wt) EBV infected AGS cells (D), and recombinant EBV infected AGS cells (E) [41]. DMSO, QST62, ISL45, and TPA/NaB stand for DMSO treatment, 62 μM isoliquiritigenin treatment, 45 μM quercetin treatment, and TPA (20 ng/mL) and NaB (3 mM) co-treatment, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4494961&req=5

Figure 7: Effects of quercetin or isoliquiritigenin on EBV protein productionEBV Protein levels were assessed by Western blot assay using anti-EBV EBNA1, BZLF1 and LMP2A antibodies to define if treatments of quercetin or isoliquiritigenin affect EBV translation in SNU719 or AGS cells. (A) The effects of treatments of quercetin or isoliquritigenin on EBV protein expression in SNU719 cells. Treatments were conducted for 48 h. GAPDH was used as an internal control in the western blot analysis. ISL and QST stands for isoliquiritigenin (62 μM) and quercetin (45 μM), respectively. (B) Time kinetics of effects of quercetin and isoliquritigenin on EBV protein production in SNU719 cells. Treatments were conducted for 0 h, 24 h and 48 h. D, Q, I and T/N stands for treatments of DMSO, quercetin (45 μM), isoliquritigenin (62 μM) and TPA (20 ng/mL) /NaB (3 mM), respectively. (C, D, E) The effect of EBV infection on the expression of EBV protein expression in EBV-negative AGS cells (C), wild type (wt) EBV infected AGS cells (D), and recombinant EBV infected AGS cells (E) [41]. DMSO, QST62, ISL45, and TPA/NaB stand for DMSO treatment, 62 μM isoliquiritigenin treatment, 45 μM quercetin treatment, and TPA (20 ng/mL) and NaB (3 mM) co-treatment, respectively.
Mentions: Similar to the transcription assay, we were interested in whether the expression of EBV protein was also affected by quercetin or isoliquiritigenin treatments. To analyze EBV protein expression, Western blot assay using anti-EBV EBNA1, BZLF1, and LMP2A antibodies was conducted with SNU719 treated either quercetin or isoliquiritigenin for 48 h. Like transcription patterns of EBV genes affected by both compounds, the Western assay showed that quercetin did enhance BZLF1 and LMP2A expressions, however, isoliquiritigenin remarkably induced LMP2A expressions (Figure 7A). In addition, in order to define time kinetics of effects of quercetin and isoliquritigenin on EBV protein production, the effects by the two compounds were determined on time course of SNU719 treated with quercetin or isoliquritigenin. During 48 h time course, quercetin treatment enhanced BZLF1 expression, yet suppressed EBNA1 expression. In contrast, isoliquiritigenin treatment exhibited little effect on BZLF1 expression and EBNA1 expression during the time course except 24 h post treatment (Figure 7B).

Bottom Line: Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth.Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency.These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and Institute of Microorganisms, Kyungpook National University, Daegu, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus