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Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts
Journal of Functional Foods ( IF 5.6 ) Pub Date : 2018-01-10 , DOI: 10.1016/j.jff.2018.01.004
Dong-eun Kim , Sunhee Jung , Hyung Won Ryu , Miri Choi , Mingu Kang , Hyunju Kang , Heung Joo Yuk , Hyejeong Jeong , Jiyeon Baek , Jae-Hyoung Song , Janghwan Kim , Hyojeung Kang , Sang-Bae Han , Sei-Ryang Oh , Sungchan Cho

Lytic induction of latent Epstein-Barr virus (EBV) has been considered as a therapeutic approach for efficient treatment of EBV-associated malignancies. Here, we established a robust assay system quantitatively measuring EBV lytic induction and identified three Euphorbia extracts as strong inducers from a screen of Korean medicinal plant extracts library. Expression of lytic genes were efficiently induced by each Euphorbia extract in SNU-719 (EBV-positive gastric carcinoma cells). Euphorbia pekinensis, out of three extracts, exhibited the most potent lytic-inducing activity. Importantly, treatment with E. pekinensis extract led to an obvious cytotoxic effect on SNU-719 cells, but little on MKN-74 cells (EBV-negative gastric carcinoma cells), indicating the selective oncolytic effect on EBV-positive gastric carcinoma. We further revealed that lytic-inducing activity of E. pekinensis was mediated by PKC/MEK signal. Moreover, we defined two structural analogs of PMA with strong lytic-inducing activity, suggesting their therapeutic applicability for the treatment of EBV-associated gastric carcinoma.

更新日期:2018-01-10
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