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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 frequency of use of EBV promotersReverse transcription followed PCR (RT-PCR) assay was conducted to determine if treatments of quercertin or isoliquiritigenin affect on frequency of use of EBV promoters in SNU719 cells. (A) KEM1 control cells specific to EBV type I showed high frequency of use of Qp and Fp. KEM3 control cells specific to EBV type III demonstrate high frequency of use of Cp/Wp. (B) Treatment of quercetin (62 μM) intensively increased frequency of use of EBV Fp, compared to that of EBV Qp in SNU719 cells. However, treatment of isoliquiritigenin (45 μM) intensively increased frequency of use of EBV Q promoter, compared to that of EBV Fp promoter in SNU719 cells. Cp, Wp, Qp, and Fp stand for EBV promoters activated depending on EBV latency types. 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.
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Figure 8: Effects of quercetin or isoliquiritigenin on frequency of use of EBV promotersReverse transcription followed PCR (RT-PCR) assay was conducted to determine if treatments of quercertin or isoliquiritigenin affect on frequency of use of EBV promoters in SNU719 cells. (A) KEM1 control cells specific to EBV type I showed high frequency of use of Qp and Fp. KEM3 control cells specific to EBV type III demonstrate high frequency of use of Cp/Wp. (B) Treatment of quercetin (62 μM) intensively increased frequency of use of EBV Fp, compared to that of EBV Qp in SNU719 cells. However, treatment of isoliquiritigenin (45 μM) intensively increased frequency of use of EBV Q promoter, compared to that of EBV Fp promoter in SNU719 cells. Cp, Wp, Qp, and Fp stand for EBV promoters activated depending on EBV latency types. 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.

Mentions: Because both quercetin and isoliquiritigenin affected expression of most EBV genes, it was questioned whether quercetin or isoliquiritigenin affected the frequency of use of EBV latency promoters such as Cp, Qp, and Fp [2]. As controls, KEM1 cells (EBV latency type 1-positive cells) showed a high frequency of use of Q and F promoters (Figure 9A) [47]. KEM3 cells specific to EBV type III demonstrated high frequency of use of C/W promoters (Figure 8A) [47]. Quercetin treatment significantly decreased frequency of use of Q promoter and increased frequency of use of F promoter, supporting functional role of quercetin for EBV lytic reactivation (Figure 8B). By contrast, isoliquiritigenin treatment clearly decreased frequency of use of F promoter and increased frequency of use of Q promoter, supporting functional role of isoliquiritigenin for EBV latency establishment (Figure 8B).


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 frequency of use of EBV promotersReverse transcription followed PCR (RT-PCR) assay was conducted to determine if treatments of quercertin or isoliquiritigenin affect on frequency of use of EBV promoters in SNU719 cells. (A) KEM1 control cells specific to EBV type I showed high frequency of use of Qp and Fp. KEM3 control cells specific to EBV type III demonstrate high frequency of use of Cp/Wp. (B) Treatment of quercetin (62 μM) intensively increased frequency of use of EBV Fp, compared to that of EBV Qp in SNU719 cells. However, treatment of isoliquiritigenin (45 μM) intensively increased frequency of use of EBV Q promoter, compared to that of EBV Fp promoter in SNU719 cells. Cp, Wp, Qp, and Fp stand for EBV promoters activated depending on EBV latency types. 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.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: Effects of quercetin or isoliquiritigenin on frequency of use of EBV promotersReverse transcription followed PCR (RT-PCR) assay was conducted to determine if treatments of quercertin or isoliquiritigenin affect on frequency of use of EBV promoters in SNU719 cells. (A) KEM1 control cells specific to EBV type I showed high frequency of use of Qp and Fp. KEM3 control cells specific to EBV type III demonstrate high frequency of use of Cp/Wp. (B) Treatment of quercetin (62 μM) intensively increased frequency of use of EBV Fp, compared to that of EBV Qp in SNU719 cells. However, treatment of isoliquiritigenin (45 μM) intensively increased frequency of use of EBV Q promoter, compared to that of EBV Fp promoter in SNU719 cells. Cp, Wp, Qp, and Fp stand for EBV promoters activated depending on EBV latency types. 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.
Mentions: Because both quercetin and isoliquiritigenin affected expression of most EBV genes, it was questioned whether quercetin or isoliquiritigenin affected the frequency of use of EBV latency promoters such as Cp, Qp, and Fp [2]. As controls, KEM1 cells (EBV latency type 1-positive cells) showed a high frequency of use of Q and F promoters (Figure 9A) [47]. KEM3 cells specific to EBV type III demonstrated high frequency of use of C/W promoters (Figure 8A) [47]. Quercetin treatment significantly decreased frequency of use of Q promoter and increased frequency of use of F promoter, supporting functional role of quercetin for EBV lytic reactivation (Figure 8B). By contrast, isoliquiritigenin treatment clearly decreased frequency of use of F promoter and increased frequency of use of Q promoter, supporting functional role of isoliquiritigenin for EBV latency establishment (Figure 8B).

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