Genipin as a novel chemical activator of EBV lytic cycle

Myoungki Son; Minjung Lee; Eunhyun Ryu; Aree Moon; Choon-Sik Jeong; Yong Woo Jung; Gyu Hwan Park; Gi-Ho Sung; Hyosun Cho; Hyojeung Kang

doi:10.1007/s12275-015-4672-9

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Genipin as a novel chemical activator of EBV lytic cycle: Myoungki Son ¹, Minjung Lee ¹, Eunhyun Ryu ¹, Aree Moon ², Choon-Sik Jeong ², Yong Woo Jung ³, Gyu Hwan Park ¹, Gi-Ho Sung ⁴, Hyosun Cho ², Hyojeung Kang ¹; Journal of Microbiology 2015;53(2):155-165.
DOI: https://doi.org/10.1007/s12275-015-4672-9
Published online: January 28, 2015

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 Korea¹College 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

Corresponding author: Hyosun Cho , Tel: +82-53-950-8569,
Hyojeung Kang , Tel: +82-53-950-8569,

Received: 26 November 2014 • Revised: 11 December 2014 • Accepted: 12 December 2014

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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.

Keywords: genipin;Epstein-Barr virus;lytic activation;methylation

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Genipin as a novel chemical activator of EBV lytic cycle

J. Microbiol. 2015;53(2):155-165. Published online January 28, 2015

DOI: https://doi.org/10.1007/s12275-015-4672-9

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