| Title | Genipin as a novel chemical activator of EBV lytic cycle |
|---|---|
| Author | Myoungki Son1, Minjung Lee1, Eunhyun Ryu1, Aree Moon2, Choon-Sik Jeong2, Yong Woo Jung3, Gyu Hwan Park1, Gi-Ho Sung4, Hyosun Cho2*, and Hyojeung Kang1* |
| Address | 1College of Pharmacy and Institute of Microorganisms, Kyungpook National University, Daegu 702-701, Republic of Korea, 2College of Pharmacy and Innovative Drug Center, Duksung Women's University, Seoul 132-714, Republic of Korea, 3College of Pharmacy, Korea University, Seoul 136-701, Republic of Korea, 4Institute for Bio-Medical Convergence, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon 404-834, Republic of Korea |
| Bibliography | Journal of Microbiology, 53(2),155-165, 2015, |
| DOI | 10.1007/s12275-015-4672-9 |
| Key Words | genipin, Epstein-Barr virus, lytic activation, methylation |
| Abstract | 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 μM), 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. |