Limits...
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 progeny productionIntracellular and extracellular EBV genome copy numbers in SNU719 cells were determined by following methods previously described to evaluate antiviral effects of quercetin and isoliquritingenin on EBV progeny production. (A) Compared to DMSO treatment (negative control), EBV intracellular copy numbers were not changed by treatments of quercetin (62 μM) or isoliquiritigenin (45 μM). (B) Compared to DMSO treatment (negative control), EBV extracellular copy numbers were remarkably increased by quercetin treatment, while the copy numers were not affected by isoliquiritigenin. Intracellular and extracellular copy numbers were calculated as relative intracellular (relative to Actin) and extracellular (relative to blank treatment) EBV genome copy numbers, respectively. Statistical significance is when the P-value is < 0.05 (95% confidence). NaB/TPA treatment stands for 1 mM treatment of NaB and 1 ng/ml treatment of TPA. ISL and QST stands for isoliquiritigenin and quercetin, respectively. (C) Time kinetics of effects of quercetin and isoliquritigenin on EBV progeny production in SNU719 cells. During 48 h time course, quercetin treatment showed to significantly enhance EBV progency production since 24 h post treatment. 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

License
getmorefigures.php?uid=PMC4494961&req=5

Figure 10: Effects of quercetin or isoliquiritigenin on EBV progeny productionIntracellular and extracellular EBV genome copy numbers in SNU719 cells were determined by following methods previously described to evaluate antiviral effects of quercetin and isoliquritingenin on EBV progeny production. (A) Compared to DMSO treatment (negative control), EBV intracellular copy numbers were not changed by treatments of quercetin (62 μM) or isoliquiritigenin (45 μM). (B) Compared to DMSO treatment (negative control), EBV extracellular copy numbers were remarkably increased by quercetin treatment, while the copy numers were not affected by isoliquiritigenin. Intracellular and extracellular copy numbers were calculated as relative intracellular (relative to Actin) and extracellular (relative to blank treatment) EBV genome copy numbers, respectively. Statistical significance is when the P-value is < 0.05 (95% confidence). NaB/TPA treatment stands for 1 mM treatment of NaB and 1 ng/ml treatment of TPA. ISL and QST stands for isoliquiritigenin and quercetin, respectively. (C) Time kinetics of effects of quercetin and isoliquritigenin on EBV progeny production in SNU719 cells. During 48 h time course, quercetin treatment showed to significantly enhance EBV progency production since 24 h post treatment. 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: Because most EBV genes tested were regulated by quercetin or isoliquiritigenin, we next asked whether these two compounds stimulated EBV progeny production. Therefore, EBV intracellular and extracellular genome copy numbers were evaluated using previous described methods [14, 29]. Intracellular EBV genome copy numbers were not affected by treatments with either quercetin or isoliquiritigenin (Figure 10A), but extracellular EBV genome copy numbers were significantly increased up to 150% by quercetin treatment (Figure 10B). In addition, in order to define time kinetics of effects of quercetin or isoliquritigenin on EBV progeny production, the effects by two compounds were determined on time course of SNU719 cells treated with quercetin or isoliquritigenin. During 48 h time course, quercetin treatment significantly enhanced EBV progency production since 24 h post treatment. In contrast, isoliquiritigenin treatment exhibited almost no effects on EBV progeny production during the time course (Figure 10C). These results indicated that quercetin is likely to derive EBV lytic replication and subsequently to produce EBV progenies from SNU719 cells.


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 progeny productionIntracellular and extracellular EBV genome copy numbers in SNU719 cells were determined by following methods previously described to evaluate antiviral effects of quercetin and isoliquritingenin on EBV progeny production. (A) Compared to DMSO treatment (negative control), EBV intracellular copy numbers were not changed by treatments of quercetin (62 μM) or isoliquiritigenin (45 μM). (B) Compared to DMSO treatment (negative control), EBV extracellular copy numbers were remarkably increased by quercetin treatment, while the copy numers were not affected by isoliquiritigenin. Intracellular and extracellular copy numbers were calculated as relative intracellular (relative to Actin) and extracellular (relative to blank treatment) EBV genome copy numbers, respectively. Statistical significance is when the P-value is < 0.05 (95% confidence). NaB/TPA treatment stands for 1 mM treatment of NaB and 1 ng/ml treatment of TPA. ISL and QST stands for isoliquiritigenin and quercetin, respectively. (C) Time kinetics of effects of quercetin and isoliquritigenin on EBV progeny production in SNU719 cells. During 48 h time course, quercetin treatment showed to significantly enhance EBV progency production since 24 h post treatment. 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

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

Figure 10: Effects of quercetin or isoliquiritigenin on EBV progeny productionIntracellular and extracellular EBV genome copy numbers in SNU719 cells were determined by following methods previously described to evaluate antiviral effects of quercetin and isoliquritingenin on EBV progeny production. (A) Compared to DMSO treatment (negative control), EBV intracellular copy numbers were not changed by treatments of quercetin (62 μM) or isoliquiritigenin (45 μM). (B) Compared to DMSO treatment (negative control), EBV extracellular copy numbers were remarkably increased by quercetin treatment, while the copy numers were not affected by isoliquiritigenin. Intracellular and extracellular copy numbers were calculated as relative intracellular (relative to Actin) and extracellular (relative to blank treatment) EBV genome copy numbers, respectively. Statistical significance is when the P-value is < 0.05 (95% confidence). NaB/TPA treatment stands for 1 mM treatment of NaB and 1 ng/ml treatment of TPA. ISL and QST stands for isoliquiritigenin and quercetin, respectively. (C) Time kinetics of effects of quercetin and isoliquritigenin on EBV progeny production in SNU719 cells. During 48 h time course, quercetin treatment showed to significantly enhance EBV progency production since 24 h post treatment. 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: Because most EBV genes tested were regulated by quercetin or isoliquiritigenin, we next asked whether these two compounds stimulated EBV progeny production. Therefore, EBV intracellular and extracellular genome copy numbers were evaluated using previous described methods [14, 29]. Intracellular EBV genome copy numbers were not affected by treatments with either quercetin or isoliquiritigenin (Figure 10A), but extracellular EBV genome copy numbers were significantly increased up to 150% by quercetin treatment (Figure 10B). In addition, in order to define time kinetics of effects of quercetin or isoliquritigenin on EBV progeny production, the effects by two compounds were determined on time course of SNU719 cells treated with quercetin or isoliquritigenin. During 48 h time course, quercetin treatment significantly enhanced EBV progency production since 24 h post treatment. In contrast, isoliquiritigenin treatment exhibited almost no effects on EBV progeny production during the time course (Figure 10C). These results indicated that quercetin is likely to derive EBV lytic replication and subsequently to produce EBV progenies from SNU719 cells.

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