Resveratrol Inhibits Proliferation and Survival of Epstein Barr Virus-Infected Burkitt's Lymphoma Cells Depending on Viral Latency Program
Resveratrol Inhibits Proliferation and Survival of Epstein Barr Virus-Infected Burkitt's Lymphoma Cells Depending on Viral Latency Program
复制标题
DOI：
10.1158/1541-7786.mcr-11-0145
复制
发表时间：
2011-10-01
影响因子：
5.2
通讯作者：
Mattia, Elena
中科院分区：
文献类型：
--
作者：
De Leo, Alessandra;Arena, Giuseppe;Mattia, Elena
白藜芦醇（3,4',5-三羟基-反式二苯乙烯）是一种多酚天然产物，具有针对多种癌症、心脏病、炎症和病毒感染的化学预防特性。 EB 病毒 (EBV) 是一种 g 疱疹病毒，会导致多种人类癌症的发生，包括伯基特淋巴瘤 (BL)。在这项研究中，我们询问白藜芦醇治疗是否会影响表现出不同潜伏期的 EBV 阳性 BL 细胞的活力。我们在此报告，无论 EBV 状态如何，白藜芦醇都会通过将细胞周期进程阻滞在 G(1) 期来诱导 caspase 依赖性细胞凋亡。然而，白藜芦醇强烈诱导 EBV(-) 和潜伏期 I EBV(+) 细胞凋亡，而潜伏期 II 和潜伏期 III EBV(+) BL 细胞显示出生存优势，该优势随着病毒基因表达模式的程度而增加。白藜芦醇诱导的细胞周期停滞和细胞凋亡与 p38 MAPK 磷酸化的诱导和 ERK1/2 信号通路的抑制有关。此外，除 EBV (+) 潜伏期 III 细胞外，所有 BL 系中 NF-kappa B DNA 结合活性均受到抑制。在潜伏期 III 表型中表达的 LMP1 癌基因与白藜芦醇抗增殖作用的较高抵抗力有关，因为 siRNA 介导的 LMP1 抑制大大增加了潜伏期 III BL 细胞以及潜伏期 III BL 细胞的敏感性。 淋巴母细胞系多酚。我们认为，白藜芦醇/siRNA 联合策略可能是治疗 EBV 相关 B 细胞恶性肿瘤的一种新方法，其中病毒基因表达模式已被确定。摩尔癌症研究中心； 9(10)； 1346-55。 (C) 2011 年 AACR。
Resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenolic natural product, shows chemopreventive properties against several cancers, heart diseases, inflammation, and viral infections. Epstein Barr virus (EBV), a g-herpesvirus, contributes to the development of several human cancers including Burkitt's lymphoma (BL). In this study, we asked whether treatment with resveratrol would affect the viability of EBV-positive BL cells displaying different forms of latency. We report here that resveratrol, regardless of EBV status, induces caspase-dependent apoptosis by arresting cell-cycle progression in G(1) phase. However, resveratrol strongly induced apoptosis in EBV(-) and latency I EBV(+) cells, whereas latency II and latency III EBV(+) BL cells showed a survival advantage that increased with the extent of the pattern of viral gene expression. Resveratrol-induced cell-cycle arrest and apoptosis occurred in association with induction of p38 MAPK phosphorylation and suppression of ERK1/2 signaling pathway. Moreover, NF-kappa B DNA-binding activity was inhibited in all BL lines except EBV (+) latency III cells.LMP1 oncogene, which is expressed in latency III phenotype, is involved with the higher resistance to the antiproliferative effect of resveratrol because siRNA-mediated inhibition of LMP1 greatly increased the sensitivity of latency III BL cells as well as that of lymphoblastoid cell lines to the polyphenol. We propose that a combined resveratrol/siRNA strategy may be a novel approach for the treatment of EBV-associated B-cell malignancies in which the viral pattern of gene expression has been defined. Mol Cancer Res; 9(10); 1346-55. (C) 2011 AACR.