Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts

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

doi:10.1016/j.jff.2018.01.004

Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts

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

Korea Research Institute of Bioscience and Biotechnology
Chungbuk National University
Kangwon National University
University of Science and Technology UST

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	146-158
Number of pages	13
Journal	Journal of Functional Foods
Volume	42
DOIs	https://doi.org/10.1016/j.jff.2018.01.004
State	Published - Mar 2018

Keywords

EBV-associated gastric carcinoma
Epstein-Barr virus
Euphorbia
Lytic induction
Medicinal plant extracts

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10.1016/j.jff.2018.01.004

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Kim, D. E., Jung, S., Ryu, H. W., Choi, M., Kang, M., Kang, H., Yuk, H. J., Jeong, H., Baek, J., Song, J. H., Kim, J., Kang, H., Han, S. B., Oh, S. R., & Cho, S. (2018). Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts. Journal of Functional Foods, 42, 146-158. https://doi.org/10.1016/j.jff.2018.01.004

@article{882d0b0872a24572a9044208dab138b9,

title = "Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts",

abstract = "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.",

keywords = "EBV-associated gastric carcinoma, Epstein-Barr virus, Euphorbia, Lytic induction, Medicinal plant extracts",

author = "Kim, \{Dong eun\} and Sunhee Jung and Ryu, \{Hyung Won\} and Miri Choi and Mingu Kang and Hyunju Kang and Yuk, \{Heung Joo\} and Hyejeong Jeong and Jiyeon Baek and Song, \{Jae Hyoung\} and Janghwan Kim and Hyojeung Kang and Han, \{Sang Bae\} and Oh, \{Sei Ryang\} and Sungchan Cho",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",

year = "2018",

month = mar,

doi = "10.1016/j.jff.2018.01.004",

language = "English",

volume = "42",

pages = "146--158",

journal = "Journal of Functional Foods",

issn = "1756-4646",

publisher = "Elsevier Ltd.",

}

Kim, DE, Jung, S, Ryu, HW, Choi, M, Kang, M, Kang, H, Yuk, HJ, Jeong, H, Baek, J, Song, JH, Kim, J, Kang, H, Han, SB, Oh, SR & Cho, S 2018, 'Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts', Journal of Functional Foods, vol. 42, pp. 146-158. https://doi.org/10.1016/j.jff.2018.01.004

TY - JOUR

T1 - Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts

AU - Kim, Dong eun

AU - Jung, Sunhee

AU - Ryu, Hyung Won

AU - Choi, Miri

AU - Kang, Mingu

AU - Kang, Hyunju

AU - Yuk, Heung Joo

AU - Jeong, Hyejeong

AU - Baek, Jiyeon

AU - Song, Jae Hyoung

AU - Kim, Janghwan

AU - Kang, Hyojeung

AU - Han, Sang Bae

AU - Oh, Sei Ryang

AU - Cho, Sungchan

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - EBV-associated gastric carcinoma

KW - Epstein-Barr virus

KW - Euphorbia

KW - Lytic induction

KW - Medicinal plant extracts

UR - https://www.scopus.com/pages/publications/85040218665

U2 - 10.1016/j.jff.2018.01.004

DO - 10.1016/j.jff.2018.01.004

M3 - Article

AN - SCOPUS:85040218665

SN - 1756-4646

VL - 42

SP - 146

EP - 158

JO - Journal of Functional Foods

JF - Journal of Functional Foods

ER -

Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts

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