Genipin as a novel chemical activator of EBV lytic cycle
Genipin as a novel chemical activator of EBV lytic cycle
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DOI：
10.1007/s12275-015-4672-9
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发表时间：
2015-02-01
影响因子：
3
通讯作者：
Kang, Hyojeung
中科院分区：
文献类型：
--
作者：
Son, Myoungki;Lee, Minjung;Kang, Hyojeung
爱泼斯坦-巴尔病毒（EBV）是一种普遍存在的伽马疱疹病毒，可引起急性感染并建立终身潜伏期。EBV引起几种人类癌症，包括伯基特淋巴瘤、鼻咽癌和胃癌。抗病毒药物可分为杀毒剂、抗病毒化疗药物和免疫调节剂。大多数抗病毒药物作用于活跃复制的病毒，而不是它们的潜伏形式。新型抗病毒药物必须对复制型和潜伏型病毒都有效。栀子花是一种常绿开花植物，属于rubibiaceae家族，在越南，中国南方，台湾，日本，缅甸和印度最常见的野生生长。栀子苷是一种从环烯醚萜苷中提取的苷元，这种苷被称为栀子苷，在栀子花的果实中大量存在。在这项研究中，genipin被评价为一种抗肿瘤和抗病毒药物，对EBV和EBV相关胃癌（EBVaGC）产生抑制作用。在EBVaGCs之一的SNU719细胞中，genipin引起显著的细胞毒性（70 μ M），诱导EBV C启动子和肿瘤抑制基因BCL7A甲基化，阻滞细胞周期进程（S期），以剂量依赖的方式上调EBV潜伏/裂解基因，刺激EBV子代产生，激活EBV F启动子激活EBV裂解，抑制EBV感染。这些结果表明，吉尼平可能是一种有前景的抗EBV和EBVaGC的抗病毒和抗肿瘤药物。
Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that causes acute infection and establishes life-long latency. EBV causes several human cancers, including Burkitt's lymphoma, nasopharyngeal and gastric carcinoma. Antiviral agents can be categorized as virucides, antiviral chemotherapeutic agents, and immunomodulators. Most antiviral agents affect actively replicating viruses, but not their latent forms. Novel antiviral agents must be active on both the replicating and the latent forms of the virus. Gardenia jasminoides is an evergreen flowering plant belonging to the Rubiaceae family and is most commonly found growing wild in Vietnam, Southern China, Taiwan, Japan, Myanmar, and India. Genipin is an aglycone derived from an iridoid glycoside called geniposide, which is present in large quantities in the fruit of G. jasminoides. In this study, genipin was evaluated for its role as an antitumor and antiviral agent that produces inhibitory effects against EBV and EBV associated gastric carcinoma (EBVaGC). In SNU719 cells, one of EBVaGCs, genipin caused significant cytotoxicity (70 mu M), induced methylation on EBV C promoter and tumor suppressor gene BCL7A, arrested cell-cycle progress (S phases), upregulated EBV latent/lytic genes in a dose-dependent manner, stimulated EBV progeny production, activated EBV F promoter for EBV lytic activation, and suppressed EBV infection. These results indicated that genipin could be a promising candidate for antiviral and antitumor agents against EBV and EBVaGC.