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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

Structures of quercetin or isoliquiritigeninCytotoxicity assay was conducted using cell counting assay (CCK-8 kit). (A, B) 50% cytotoxicity dose (CD50) of quercetin or isoliquiritigenin against SNU719 cells were 62 μM and 45 μM, respectively. Each measurement was repeated in three times. Averages and standard errors of measurements were displayed on graphs. ISL and QST stands for isoliquiritigenin and quercetin, respectively. Molecular structures of quercetin and isoliquiritigenin were defined inside Figure 1A and 1B. (C, D) Time kinetics of cytotoxicities of quercetin and isoliquritigenin, CD50s produced by treatments of quercetin or isoliquritigenin were determined on time course. (E, F) Time course cell viabilities of SNU719 cells treated with quercetin and isoliquiritigenin using cell viability assay using trypan blue staining. Cell viability was calculated as percentage of live cells relative to total cells. DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively.
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Figure 1: Structures of quercetin or isoliquiritigeninCytotoxicity assay was conducted using cell counting assay (CCK-8 kit). (A, B) 50% cytotoxicity dose (CD50) of quercetin or isoliquiritigenin against SNU719 cells were 62 μM and 45 μM, respectively. Each measurement was repeated in three times. Averages and standard errors of measurements were displayed on graphs. ISL and QST stands for isoliquiritigenin and quercetin, respectively. Molecular structures of quercetin and isoliquiritigenin were defined inside Figure 1A and 1B. (C, D) Time kinetics of cytotoxicities of quercetin and isoliquritigenin, CD50s produced by treatments of quercetin or isoliquritigenin were determined on time course. (E, F) Time course cell viabilities of SNU719 cells treated with quercetin and isoliquiritigenin using cell viability assay using trypan blue staining. Cell viability was calculated as percentage of live cells relative to total cells. DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively.

Mentions: As molecular structures of quercetin and isoliquiritigenin are similar each other, antitumor activities of quercetin was compared with those of isoliquiritigenin. In order to determine 50% cytotoxicity dose of quercetin or isoliquiritigenin against EBV associated gastric carcinoma cell line SNU719 cells, cellular cytotoxicity assay was conducted with Cell Counting Kit-8 (CCK-8) (Dojindo). CCK-8 allows for sensitive colorimetric assay determination of the number of viable cells in cell proliferation and cytotoxicity assays. 50% cytotoxicity dose (CD50) of quercetin and isoliquiritigenin against SNU719 were 62 μM and 45 μM, respectively (Figure 1A and 1B). In addition, in order to define time kinetics of cytotoxicities of quercetin and isoliquritigenin, CD50s produced by each compound treatment were determined on time course. During 48 h time course, CD50s were decreased from undetectable levels to values presented above (Figure 1C and 1D). Cell viability was also determined on time course in SNU719 cells treated with quercetin or isoliquiritigenin using cell viability assay using trypan blue staining. Although quercetin treatment showed slightly lower cell viability compared to the treatments of DMSO or isoliquritigenin, all treatments exhibited more than 85% of cell viability during the 48 h time course (Figure 1E and 1F).


Quercetin-induced apoptosis prevents EBV infection.

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

Structures of quercetin or isoliquiritigeninCytotoxicity assay was conducted using cell counting assay (CCK-8 kit). (A, B) 50% cytotoxicity dose (CD50) of quercetin or isoliquiritigenin against SNU719 cells were 62 μM and 45 μM, respectively. Each measurement was repeated in three times. Averages and standard errors of measurements were displayed on graphs. ISL and QST stands for isoliquiritigenin and quercetin, respectively. Molecular structures of quercetin and isoliquiritigenin were defined inside Figure 1A and 1B. (C, D) Time kinetics of cytotoxicities of quercetin and isoliquritigenin, CD50s produced by treatments of quercetin or isoliquritigenin were determined on time course. (E, F) Time course cell viabilities of SNU719 cells treated with quercetin and isoliquiritigenin using cell viability assay using trypan blue staining. Cell viability was calculated as percentage of live cells relative to total cells. DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Structures of quercetin or isoliquiritigeninCytotoxicity assay was conducted using cell counting assay (CCK-8 kit). (A, B) 50% cytotoxicity dose (CD50) of quercetin or isoliquiritigenin against SNU719 cells were 62 μM and 45 μM, respectively. Each measurement was repeated in three times. Averages and standard errors of measurements were displayed on graphs. ISL and QST stands for isoliquiritigenin and quercetin, respectively. Molecular structures of quercetin and isoliquiritigenin were defined inside Figure 1A and 1B. (C, D) Time kinetics of cytotoxicities of quercetin and isoliquritigenin, CD50s produced by treatments of quercetin or isoliquritigenin were determined on time course. (E, F) Time course cell viabilities of SNU719 cells treated with quercetin and isoliquiritigenin using cell viability assay using trypan blue staining. Cell viability was calculated as percentage of live cells relative to total cells. DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively.
Mentions: As molecular structures of quercetin and isoliquiritigenin are similar each other, antitumor activities of quercetin was compared with those of isoliquiritigenin. In order to determine 50% cytotoxicity dose of quercetin or isoliquiritigenin against EBV associated gastric carcinoma cell line SNU719 cells, cellular cytotoxicity assay was conducted with Cell Counting Kit-8 (CCK-8) (Dojindo). CCK-8 allows for sensitive colorimetric assay determination of the number of viable cells in cell proliferation and cytotoxicity assays. 50% cytotoxicity dose (CD50) of quercetin and isoliquiritigenin against SNU719 were 62 μM and 45 μM, respectively (Figure 1A and 1B). In addition, in order to define time kinetics of cytotoxicities of quercetin and isoliquritigenin, CD50s produced by each compound treatment were determined on time course. During 48 h time course, CD50s were decreased from undetectable levels to values presented above (Figure 1C and 1D). Cell viability was also determined on time course in SNU719 cells treated with quercetin or isoliquiritigenin using cell viability assay using trypan blue staining. Although quercetin treatment showed slightly lower cell viability compared to the treatments of DMSO or isoliquritigenin, all treatments exhibited more than 85% of cell viability during the 48 h time course (Figure 1E and 1F).

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