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

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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

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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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