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 apoptosisFITC Annexin V Apoptosis Detection assay and Western blot assay were conducted. (A) The effect of quercetin or isoliquiritigenin on early apoptosis (far left), necrosis/late apoptosis (middle) and membrane integrity (far right) in SNU719. DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively. Statistical significance is when the P-value is < 0.05 (95% confidence). (B, C) The effect of quercetin or isoliquiritigenin on the expression of PARP (B) and phospho-JNK (C). DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively. TPA/NaB is positive control. (D, E) The effect of co-treatment of SP600125 (10 μM, inhibitor of JNK kinase) with quercetin or isoliquiritigenin on the expression of phospho-JNK (D) and PARP (E). (F, G, H) The effect of EBV infection on the expression of cleaved PARP and Phospho-JNK in EBV-negative AGS cells (F), wild type (wt) EBV infected AGS cells (G), and recombinant EBV infected AGS cells (H) [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

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

Figure 2: Effects of quercetin or isoliquiritigenin on apoptosisFITC Annexin V Apoptosis Detection assay and Western blot assay were conducted. (A) The effect of quercetin or isoliquiritigenin on early apoptosis (far left), necrosis/late apoptosis (middle) and membrane integrity (far right) in SNU719. DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively. Statistical significance is when the P-value is < 0.05 (95% confidence). (B, C) The effect of quercetin or isoliquiritigenin on the expression of PARP (B) and phospho-JNK (C). DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively. TPA/NaB is positive control. (D, E) The effect of co-treatment of SP600125 (10 μM, inhibitor of JNK kinase) with quercetin or isoliquiritigenin on the expression of phospho-JNK (D) and PARP (E). (F, G, H) The effect of EBV infection on the expression of cleaved PARP and Phospho-JNK in EBV-negative AGS cells (F), wild type (wt) EBV infected AGS cells (G), and recombinant EBV infected AGS cells (H) [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: Two apoptosis assays as FITC Annexin V Apoptosis Detection assay and Western blot assay using anti-PARP antibody were conducted to analyze effects of quercetin or isoliquiritigenin on apoptosis and membrane integrity. First, FITC Annexin V Apoptosis detection assay was conducted to analyze cytotoxic effects on early apoptosis, necrosis/late apoptosis, and membrane integrity of SNU719 cells treated either quercetin or isoliquiritigenin for 48 h. Quercetin treatment induced significantly more early apoptosis and necrosis/late apoptosis in SNU719 cells than isoliquiritigenin treatment. Compared to DMSO treatment, quercetin treatment showed to induce early apoptosis approximately up to 175% and necrosis/late apoptosis up to 215%, whereas isoliquiritigenin treatment did not cause significant differences (Figure 2A, Supplemental Figure 1). However, membrane integrity of SNU719 cells was not affected by quercetin or isoliquiritigenin treatments, compared to DMSO treatment (Figure 2A, Supplemental Figure 1). These results indicated that quercetin and isoliquiritigenin did induce apoptosis without disrupting membrane integrity of 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 apoptosisFITC Annexin V Apoptosis Detection assay and Western blot assay were conducted. (A) The effect of quercetin or isoliquiritigenin on early apoptosis (far left), necrosis/late apoptosis (middle) and membrane integrity (far right) in SNU719. DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively. Statistical significance is when the P-value is < 0.05 (95% confidence). (B, C) The effect of quercetin or isoliquiritigenin on the expression of PARP (B) and phospho-JNK (C). DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively. TPA/NaB is positive control. (D, E) The effect of co-treatment of SP600125 (10 μM, inhibitor of JNK kinase) with quercetin or isoliquiritigenin on the expression of phospho-JNK (D) and PARP (E). (F, G, H) The effect of EBV infection on the expression of cleaved PARP and Phospho-JNK in EBV-negative AGS cells (F), wild type (wt) EBV infected AGS cells (G), and recombinant EBV infected AGS cells (H) [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

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

Figure 2: Effects of quercetin or isoliquiritigenin on apoptosisFITC Annexin V Apoptosis Detection assay and Western blot assay were conducted. (A) The effect of quercetin or isoliquiritigenin on early apoptosis (far left), necrosis/late apoptosis (middle) and membrane integrity (far right) in SNU719. DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively. Statistical significance is when the P-value is < 0.05 (95% confidence). (B, C) The effect of quercetin or isoliquiritigenin on the expression of PARP (B) and phospho-JNK (C). DMSO, QST62, and ISL45 stand for DMSO treatment, 62 μM isoliquiritigenin treatment, and 45 μM quercetin treatment, respectively. TPA/NaB is positive control. (D, E) The effect of co-treatment of SP600125 (10 μM, inhibitor of JNK kinase) with quercetin or isoliquiritigenin on the expression of phospho-JNK (D) and PARP (E). (F, G, H) The effect of EBV infection on the expression of cleaved PARP and Phospho-JNK in EBV-negative AGS cells (F), wild type (wt) EBV infected AGS cells (G), and recombinant EBV infected AGS cells (H) [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: Two apoptosis assays as FITC Annexin V Apoptosis Detection assay and Western blot assay using anti-PARP antibody were conducted to analyze effects of quercetin or isoliquiritigenin on apoptosis and membrane integrity. First, FITC Annexin V Apoptosis detection assay was conducted to analyze cytotoxic effects on early apoptosis, necrosis/late apoptosis, and membrane integrity of SNU719 cells treated either quercetin or isoliquiritigenin for 48 h. Quercetin treatment induced significantly more early apoptosis and necrosis/late apoptosis in SNU719 cells than isoliquiritigenin treatment. Compared to DMSO treatment, quercetin treatment showed to induce early apoptosis approximately up to 175% and necrosis/late apoptosis up to 215%, whereas isoliquiritigenin treatment did not cause significant differences (Figure 2A, Supplemental Figure 1). However, membrane integrity of SNU719 cells was not affected by quercetin or isoliquiritigenin treatments, compared to DMSO treatment (Figure 2A, Supplemental Figure 1). These results indicated that quercetin and isoliquiritigenin did induce apoptosis without disrupting membrane integrity of 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