RESUMO
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) has an instrumental role in maintaining EBV latent infection by controlling EBV episome replication and regulating viral transcription. It is a ubiquitously expressed protein during latent viral infection and in EBV-associated tumors. The EBNA1 C-terminus interacts functionally with the Qp and Cp that control viral gene expression in latency I/II and III, respectively. EBNA1 has been classified into five subtypes due to sequence variation in the DNA-interacting C-terminus. By DNA sequence analysis of its C-terminus, we detected a main sub-variant (V-val-v1) of EBNA1 with valine located in both positions 487 and 528 from matched samples including NPC biopsies and peripheral blood taken from Vietnamese (9), Chinese (12) NPC patients and healthy donors (5). In the FR-region of oriP from nine NPC biopsies from Vietnam we also frequently found substitutions, deletions and variable numbers of repeats. Using a luciferase reporter system, EBNA1 and FR both derived from Asian isolates induced higher transcriptional activity than those from B95-8 virus.
Assuntos
Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Variação Genética , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/virologia , Ativação Transcricional , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Linhagem Celular , China , Antígenos Nucleares do Vírus Epstein-Barr/química , Antígenos Nucleares do Vírus Epstein-Barr/genética , Genes Reporter , Herpesvirus Humano 4/classificação , Herpesvirus Humano 4/isolamento & purificação , Humanos , Mutação , Elementos de Resposta , Alinhamento de Sequência , Análise de Sequência de DNA , Transativadores/química , Transativadores/genética , Transativadores/metabolismo , VietnãRESUMO
Plants of the genus Crinum (Amaryllidaceae) are widely used in folk medicine in different tropical and subtropical regions around the world. The Indian species Crinum latifolium (L.) was traditionally used to treat rheumatism, fistula, tumors, earaches, rubefacient, tubercle and whitlow. In Vietnamese and Chinese traditional medicine Crinum latifolium preparations are used until nowadays because of their antiviral and antitumor properties. In this study, we demonstrate potent in vitro antioxidant activity of an aqueous Crinum latifolium extract by an oxygen radical absorbance capacity (ORAC) value of 1610 ± 150 µmol Trolox equivalents/g. Furthermore, significant anti-inflammatory effects of this extract were shown by its potential to suppress indoleamine 2,3-dioxygenase (IDO) mediated tryptophan degradation in unstimulated- and mitogen-stimulated PBMC at IC(50) doses of 241 ± 57 µg/ml and 92 ± 20 µg/ml, respectively. Concentrations of the immune activation marker neopterin were slightly diminished in unstimulated PBMC, whereas a dose-dependent inhibition of neopterin formation was observed in mitogen-stimulated PBMC (IC(50) = 453 ± 86 µg/ml). Additionally, we measured also dose-dependent inhibitory effects of this aqueous Crinum latifolium extract on cell proliferation of highly metastatic human prostate carcinoma PC3 cells (IC(50) = 4.5 ± 0.8 mg/ml), androgen-sensitive prostate adenocarcinoma LNCaP cells (IC(50) =2.3 ± 0.1 mg/ml), and benign prostate hyperplasia BPH-1 cells (IC(50) = 2.1 ± 0.04 mg/ml). We conclude that both effects, inhibition of tumor cell growth and recovery of immune functions, are important for the antitumor properties of Crinum latifolium.