• Title/Summary/Keyword: Epstein-Barr virus activation

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Deletion Analysis of the Major NF-${\kappa}B$ Activation Domain in Latent Membrane Protein 1 of Epstein-Barr Virus

  • Cho, Shin;Lee, Won-Keun
    • Journal of Microbiology
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    • v.37 no.4
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    • pp.256-262
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    • 1999
  • Latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) is an integral membrane protein with six transmembrane domains, which is essential for EBV-induced B cell transformation. LMP1 functions as a constitutively active tumor necrosis factor receptor (TNFR) like membrane receptor, whose signaling requires recruitment of TNFR-associated factors (TRAFs) and leads to NF-${\kappa}B$ activation. NF-${\kappa}B$ activation by LMP1 is critical for B cell transformation and has been linked to many phenotypic changes associated with EBV-induced B cell transformation. Deletion analysis has identified two NF-${\kappa}B$ activation regions in the carboxy terminal cytoplasmic domains of LMP1, termed CTAR1 (residues 194-232) and CTAR2 (351-386). The membrane proximal C-terminal domain was precisely mapped to a PXQXT motif (residues 204-208) involved in TRAF binding as well as NF-${\kappa}B$ activation. In this study, we dissected the CTAR2 region, which is the major NF-${\kappa}B$ signaling effector of LMP1, to determine a minimal functional sequence. A series of LMP1 mutant constructs systematically deleted for the CTAR2 region were prepared, and NF-${\kappa}B$ activation activity of these mutants were assessed by transiently expressing them in 293 cells and Jurkat T cells. The NF-${\kappa}B$ activation domain of CTAR2 appears to reside in a stretch of 6 amino acids (residues 379-384) at the end of the carboxy terminus.

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Anti-tumor Promoting Activity of Some Malaysian Traditional Vegetables (Ulam)

  • Mooi, L. Yang;Ali, A.M.;Norhanom, A.B.;Salleh, K. Mat;Murakami, A.;Koshimizu, K.
    • Natural Product Sciences
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    • v.5 no.1
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    • pp.33-38
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    • 1999
  • Ethanolic extracts of different parts of 10 local traditional vegetables (ulam) (Amaranthus gangeticus, Jussiaea linifolia, Eugenia polyantha, Trapa incisa, Trichosanthes anquina, Mangifera indica, Pachyrrhirus erosus, Barringtonia mcarostachya, Carica papaya, and Coleus tuberosus) were screened for in vitro antitumor promoting activity using the inhibition test of Epstein-Barr virus (EBV) activation in Raji cells induced by phorbol 12-myristate 13-acetate and sodium-n-butyrate. All the extracts were found to have strong inhibition activity toward EBV-activation, except for leaf extract of T. anquina. The extracts were non-cytotoxic to the Raji cells except for the extracts of A. gangeticus (leaves), B. macrostachya (leaves), E. polyantha (young leaves), and J. linifolia (leaves) where the viability of the cells were decreased significantly.

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Interference of Fisetin with Targets of the Nuclear Factor-κB Signal Transduction Pathway Activated by Epstein-Barr Virus Encoded Latent Membrane Protein 1

  • Li, Rong;Liang, Hong-Ying;Li, Ming-Yong;Lin, Chun-Yan;Shi, Meng-Jie;Zhang, Xiu-Juan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9835-9839
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    • 2014
  • Fisetin is an effective compound extracted from lacquer which has been used in the treatment of various diseases. Preliminary data indicate that it also exerts specific anti-cancer effects. However, the manner in which fisetin regulates cancer growth remains unknown. In this study, we elucidated interference of fisetin with targets of the nuclear factor ${\kappa}B$ signal transduction pathway activated by Epstein-Barr virus encoding latent membrane protein 1 (LMP1)in nasopharyngeal carcinoma (NPC) cells, Results showed that fisetin inhibited the survival rate of CNE-LMP1 cells and NF-${\kappa}B$ activation caused by LMP1. Fisetin also suppressed nuclear translocation of NF-${\kappa}B$ (p65) and $I{\kappa}B{\alpha}$ phosphorylation, while inhibiting CyclinD1, all key targets of the NF-${\kappa}B$ signal transduction pathway. It was suggested that interference effects of fisetin with signal transduction activated by LMP1 encoded by the Epstein-Barr virus may play an important role in its anticancer potential.

Isolation and Identification of Antitumor Promoters from the Seeds of Cassia tora

  • Park, Yeung-Beom;Kim, Seon-Bong
    • Journal of Microbiology and Biotechnology
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    • v.21 no.10
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    • pp.1043-1048
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    • 2011
  • A methanol extract of Cassia tora seeds was successively partitioned with diethyl ether, chloroform, ethyl acetate, and water, and the antitumor-promoting activity of the solvent fractions was determined by inhibition of Epstein-Barr virus early antigen (EBV-EA) activation induced by teleocidin B-4 in Raji cells. The diethyl ether (68.7%) and chloroform (91.2%) fractions and the hydrolysate (94.3%) of the ethyl acetate fraction had strong inhibitory activities. The chloroform and ethyl acetate fractions were chromatographed on silica gel and further purified by HPLC. Three active compounds, obtusifolin-2-glucoside (75.0%), chryso-obtusin-6-glucoside (56.8%), and norrubrofusarin-6-glucoside (39.4%), were obtained from the ethyl acetate fraction, and two active compounds, questin (97.9%) and chryso-obtusin (53.8%), were isolated from the chloroform fraction.

Anti-tumor Promoting Activity of Some Malaysian Traditional Vegetable (Ulam) Extracts by Immunoblotting Analysis of Raji Cells

  • Ali, A.M.;Mooi, L.Y.;Yih, K. Yih;Norhanom, A.W.;Saleh, K. Mat;Lajis, N.H.;Yazid, A.M.;Ahmad, F.B.H.;Prasad, U.
    • Natural Product Sciences
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    • v.6 no.3
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    • pp.147-150
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    • 2000
  • The extracts of Carica papaya (flower), Barringtonia macrostachya (leaves), Coleus tuberosus (tuber), Mangifera indica (fruit skin) and Eugenia polyantha (leaves) showed strong in vitro anti-tumor promoting activity when assayed using Raji cells (Mooi et al., 1999). The antitumor promoting activity of the crude extracts was further analyzed by immunoblotting analysis of Raji cells carving Epstein-Barr virus genome. The expression of early antigens diffuse (EA-D) and early antigens restricted (EA-R) was determined by performing western blotting of treated Raji cells with human sera of nasopharyngeal carcinoma patients. All the plant extracts were shown to be able to suppress both EA-D and EA-R.

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Tumour Promoting Activity of Plants Used in Malaysian Traditional Medicine

  • Ilham, M.;Yaday, M.;Norhanom, A.W.
    • Natural Product Sciences
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    • v.1 no.1
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    • pp.31-42
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    • 1995
  • One hundred plants in 43 families used in Malaysian traditional medicine were screened for tumour promoting activity using two methods, the technique of activation of latent Epstein-Barr Virus (EBV) in Raji cells and the irritation test on mouse ear. Extracts of only eight plants belonging to the Euphorbiaceae were found to possess EBV activation factor and to give a positive irritation test in mouse ear. These plants included Euphorbia tirucalli L., E. splendes, Jatropha podagrica, J. gossypyfolia L., Pedilanihus tithymaloides (L.) Poitt., Croton argyratus Bl., Exocoecaria agallocha L. and Codiaeum variegatum (L.) Bl. Seven of these plants are used internally in Malaysian traditional medicine. As such, they pose potential danger in the promotion of initiated cells of the mucosal tissue towards disease. Further studies are required to assess the epidemiological impact of these plants in the development of disease.

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Biological Activities of Phloroglucinol Derivatives from Eucalyptus Spp.

  • Singh, Inder Pal;Etoh, Hideo
    • Natural Product Sciences
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    • v.3 no.1
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    • pp.1-7
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    • 1997
  • Eucalyptus is a rich source of biologically active compounds. Among these, phloroglucinol compounds such as sideroxylonals, macrocarpals, euglobals, and robustadials are unique to Eucalyptus species. Sideroxylonal A is a very potent attachment-inhibitor. Macrocarpals show very strong antibacterial activity against gram positive bacteria. Macrocarpals also show HIV-RTase inhibitory activity. Euglobals are potent inhibitors of Epstein-Barr virus activation and are developed as skin and antitumor agents. They also show granulation inhibitory activity. In this review we aim to remove the existing confusion in literature on macrocarpals and discuss the biological activities and structure-activity relationships of phloroglucinol compounds.

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Susceptibility of KSHV-Infected PEL Cell Lines to the Human Complement System

  • Yoo, Seung-Min;Jeon, Hyungtaek;Lee, Suhyuk;Lee, Myung-Shin
    • Journal of Microbiology and Biotechnology
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    • v.26 no.3
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    • pp.618-626
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    • 2016
  • Pleural effusion lymphoma (PEL) is a rare B-cell lymphoma that has a very poor prognosis with a median survival time of around 6 months. PEL is caused by Kaposi's sarcoma-associated herpesvirus, and is often co-infected with the Epstein Barr virus. The complement system is fundamental in the innate immune system against pathogen invasion and tumor development. In the present study, we investigated the activation of the complement system in PEL cells using human serum complements. Interestingly, two widely used PEL cell lines, BCP-1 and BCBL-1, showed different susceptibility to the complement system, which may be due to CD46 expression on their cell membranes. Complement activation did not induce apoptosis but supported cell survival considerably. Our results demonstrated the susceptibility of PEL to the complement system and its underlying mechanisms, which would provide insight into understanding the pathogenesis of PEL.

Inhibitory Effect of Various Cereal and Bean Extracts on Carcinogenicity in vitro (곡류 및 두류 에탄올 추출물의 in vitro 발암 억제 효과 비교)

  • Choi, Yeong-Hee;Kang, Mi-Young;Nam, Seok-Hyun
    • Korean Journal of Food Science and Technology
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    • v.30 no.4
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    • pp.964-969
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    • 1998
  • To investigated the anticarcinogenic activity of 70% ethanol extracts from various cereal in vitro, antimutagenic activity, inhibitory effect of DNA strand scission and tumor promotion were examined. The antimutagenic activity of the beans such as black bean and small red bean was generally higher than that of cereals examined. However inhibitory activity of 70% ethanolic extracts against DNA strand scission induced mitomycin C showed that millet, job's tear, black bean and soy bean among cereals and beans tested in this study inhibited effectively the DNA strand scission. Antioxidative activity of some cereal extracts determined by using linoleic acid model system showed that Job's tear, millet and black bean were higher antioxidative activity than other cereals and beans. Conventional short-term antipromoter assay system using activation of Epstein Barr virus (EBV) clearly demonstrated that sorghum, buckwheat, black bean and small red bean have inhibitory effects on promotion in cellular carcinogenesis.

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Cross-linking of CD80 and CD86 Diminishes Expression of CD54 on EBV-transformed B Cells through Inactivation of RhoA and Ras

  • Park, Ga-Bin;Kim, Yeong-Seok;Song, Hyun-Keun;Kim, Seong-Han;Park, Dong-Man;Lee, Wang-Jae;Hur, Dae-Young
    • IMMUNE NETWORK
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    • v.11 no.6
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    • pp.390-398
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    • 2011
  • Background: Epstein Barr virus (EBV) infected B cells are transformed into lymphoblastoid cell lines. Some researchers suggested some a few similarities between this process and carcinogenesis. We observed the expression of CD80 and CD86, co-stimulatory molecules on EBV-transformed B cells and changes of CD54 expression after stimulation of CD80 and CD86. Methods: CD80 and CD86 were stimulated using anti-CD80 and anti-CD86 monoclonal antibodies. To assess apoptosis and surface protein expression, flow cytometric analysis was performed. Intracellular signal molecules were evaluated by RT-PCR and immunoblot. Morphology and localization of proteins were examined using inverted or confocal microscope. Results: Cross-linking of CD80 and CD86 induced apoptosis and interfered with proliferation of EBV-transformed B cells, and dispersion of clumped cells. We also examined that their stimulation induced ROS accumulation and reduced CD54 expression. Interestingly, we observed that CD80 and CD86 diminished the expression of CD54 in different methods. Both CD80 and CD86 downregulated activation of focal adhesion kinase. CD80 stimulus inhibited CD54 expression through mainly RhoA inactivation, while CD86 down-regulated Ras and JNK phosphorylation. Conclusion: These results suggest that co-stimulatory CD80 and CD86 molecules, expressed EBV-transformed B cells, may play a role in apoptosis and cell adhesion.