(-)-Epigallocatechin‑3‑gallate inhibition of Epstein‑Barr virus spontaneous lytic infection involves downregulation of latent membrane protein 1

Abstract

Abstract. The Epstein-Barr virus (EBV) lytic cycle contributes to the development of EBV-associated diseases. EBV-encoded latent membrane protein 1 (LMP1) is key to EBV lytic replication, and our previous work indicated that epigallocatechin-3-gallate (EGCG) inhibited constitutive EBV lytic infection through the suppression of LMP1-activated phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-related protein kinase 1/2 signaling. The present study demonstrated that LMP1 in CNE-LMP1 constructed cells significantly induced the expression of the EBV lytic proteins BZLF1 (P<0.001) and BMRF1 (P<0.05) compared with CNE1 cells. Following treatment with a specific DNAzyme that targets LMP1, significantly reduced protein expression levels of BZLF1 and BMRF1 in EBV-associated epithelial carcinoma CNE1-LMP1 cells (P<0.001 and P<0.01, respectively) and lymphoma B95.8 cells (both P<0.01) were observed. Furthermore, EGCG significantly inhibited the mRNA and protein expression levels of LMP1 (P<0.05) in an apparent dose-dependent manner in CNE1-LMP1 and B95.8 cells. Thus, the present findings indicated that the molecular mechanism underlying EGCG inhibition of EBV lytic infection involves downregulation of LMP1. IntroductionEpstein-Barr virus (EBV) is a human herpes virus that infects over 90% of the human population worldwide (1). EBV is suggested to be an environmental factor associated with the development of several human malignancies, including nasopharyngeal carcinoma (NPC), Burkitt's lymphoma, Hodgkin's disease (HD), gastric cancer, natural killer/T-cell lymphoma, acquired immune deficiency syndrome-and transplantation-associated lymphoma (2,3), breast carcinoma, and hepatocellular carcinoma (4,5). EBV, as all other herpes viruses, may establish a latent or lytic infection in host cells (6). Notably, studies suggest that EBV reactivation into a lytic cycle may contribute to the pathogenesis of malignancies (7,8). EBV lytic infection in vivo has been identified by elevated antibody titers against EBV lytic antigens and by increased viral DNA load in the serum/plasma, and these observations correspond with advanced cancer stages, poor prognosis or tumor recurrence following therapy (9,10). Additionally, serological studies have indicated that EBV lytic infection may occur months or years prior to a clinical diagnosis of NPC, HD or Burkitt's lymphoma, which suggests EBV lytic infection may be a risk factor for cancer development (11-13).Green tea contains (-)-epigallocatechin-3-gallate (EGCG), which is reported to have antioxidant, antibacterial and antitumor effects (14,15). EGCG has been indicated to modulate multiple signaling pathways, including the phosphoinositide 3-kinase (PI3-K)/Akt and mitogen-activated protein kinase (MAPK) signaling pathways, which may enable it to exert its cancer chemopreventive and therapeutic effects (16,17).EBV encoded latent membrane protein 1 (LMP1), which is considered to have oncogenic properties, has been identified in 90% of patients with NPC...

(−)‐Epigallocatechin‐3‐gallate induces cell apoptosis in chronic myeloid leukaemia by regulating Bcr/Abl‐mediated p38‐MAPK/JNK and JAK2/STAT3/AKT signalling pathways

“…Green tea is one of the most widely consumed teas in the world and is reported to have significant benefits to human health, which is chemically characterized by the presence of high amounts of polyphenolic compounds known as catechins. The most abundant component is epigallocatechin‐3‐gallate (EGCG), which appears to be the primary active ingredient responsible for the biological effects of green tea . EGCG has received much attention in recent years.…”

“…The most abundant component is epigallocatechin-3-gallate (EGCG), which appears to be the primary active ingredient responsible for the biological effects of green tea. 18,19 EGCG has received much attention in recent years. Previous studies have shown that EGCG exhibits antioxidative, antibacterial, and antitumor effects.…”

Matrix metalloproteinase inhibitors identified from Camellia sinensis for COVID-19 prophylaxis: an in silico approach

“…Table 5 displays the modulated pathways and their gene counts. The various studies revealed that catechins present in the Camellia sinensis, are the major polyphenols and have a potential role in several viral diseases namely: (HBV) Hepatitis B Virus (Zhong et al 2015), (HSV) Herpes Simplex Virus (Colpitts and Schang 2014), (EBV) Epstein-Barr Virus (Liu et al 2018), Adenovirus (Weber et al 2003), (HIV) Human Immunodeficiency Virus (Yamaguchi et al 2002), (HCV) Hepatitis C Virus (Ciesek et al 2011), (DENV) Dengue Virus (Ismail and Jusoh 2017), (JEV) Japanese encephalitis Virus (Ismail and Jusoh 2017), (ZIKV) Zika virus (Carneiro et al 2016), (TBEV) Tick Borne Encephalitis Virus (Ismail and Jusoh 2017), (CHIKV) Chikungunya Virus (Weber et al 2015), (HTLV-1) Human T cell Leukaemia Virus Type -1 (Harakeh et al 2014), (EV71) Enterovirus 71 (Ho et al 2009), (EBOV) Ebola Virus (Shurtleff et al 2014), (PRRSV) Porcine Reproductive and Respiratory Syndrome Virus (Zhao et al 2014), (VHSV) Hemorrhagic Septicaemia Virus (Estepa 2005), (IHNV) Hematopoietic Necrosis Virus (Estepa 2005), (SVCV) Spring Viremia Carp virus (Estepa 2005) and (GCRV) Grass Carp Reo Virus (Wang et al 2016) (Fig. 2).…”

“…Warm water decoction made by using various species in Ayurveda called ‘ Kashay’ is generally in practice in the prevention of fever, headache, common cold, and inflammation (Tillu et al 2020 ). Similarly, the warm decoction of dry or fresh leaves of Camellia sinensis with or without sugar is also used in daily life style to overcome stress and has been documented for anti-inflammatory, analgesic (De Lima MotaI et al 2015 ) and CNS stimulant activity (Rubab et al 2020 ).…”

Deoxyribozymes as Catalytic Nanotherapeutic Agents

“…It also increased apoptosis and enhanced radiosensitivity when a suboptimal dose of radiation was combined with injection of DNAzyme (83). DZ1 caused downregulation of EBV lytic proteins BZLF1 and BMRF1 (84) and reduced luciferase expressing human NPC compared with tumors treated with saline. Efficacy in response to radiotherapy was improved when DZ1 was given as adjunctive therapy to radiotherapy, demonstrating the radiosensitizing effects of DZ1 (61).…”