Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines

Hyunju Kang, Jaehyung Song, Kwangman Choi, Hyeongki Kim, Miri Choi, So Young Lee, Chonsaeng Kim, Sang Jun Lee, Moon Jung Song, Hyojeung Kang, Sung Hoon Back, Sang Bae Han, Sungchan Cho

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Lytic induction of latent Kaposi's sarcoma-associated herpesvirus (KSHV) has been considered as a therapeutic option for efficient treatment of several KSHV-associated malignancies. Here, we developed a robust high-throughput screening system that allows an easy and quantitative measurement of lytic induction of latent KSHV and discovered three anthracyclines as potent inducers from screen of FDA-approved drugs. Lytic induction of latent KSHV by three compounds was verified by the significant induction of lytic genes and subsequent production of infectious KSHV. Importantly, lytic induction by three compounds was much more efficient than that by sodium butyrate, a well-characterized inducer of KSHV lytic cycle. Mechanistically, the anthracyclines caused lytic induction of KSHV through apoptosis induced by their DNA intercalation rather than topoisomerase II inhibition. Consequently, our results clearly demonstrated a role of anthracyclines as effective lytic inducers of KSHV and also provided a molecular basis of their use for efficient treatment of diseases associated with KSHV infection.

Original languageEnglish
Pages (from-to)8515-8527
Number of pages13
JournalOncotarget
Volume5
Issue number18
Publication statusPublished - 2014 Jan 1

Fingerprint

Human Herpesvirus 8
Anthracyclines
Herpesviridae Infections
Type II DNA Topoisomerase
Butyric Acid
Apoptosis

ASJC Scopus subject areas

  • Oncology

Cite this

Kang, H., Song, J., Choi, K., Kim, H., Choi, M., Lee, S. Y., ... Cho, S. (2014). Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines. Oncotarget, 5(18), 8515-8527.

Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines. / Kang, Hyunju; Song, Jaehyung; Choi, Kwangman; Kim, Hyeongki; Choi, Miri; Lee, So Young; Kim, Chonsaeng; Lee, Sang Jun; Song, Moon Jung; Kang, Hyojeung; Back, Sung Hoon; Han, Sang Bae; Cho, Sungchan.

In: Oncotarget, Vol. 5, No. 18, 01.01.2014, p. 8515-8527.

Research output: Contribution to journalArticle

Kang, H, Song, J, Choi, K, Kim, H, Choi, M, Lee, SY, Kim, C, Lee, SJ, Song, MJ, Kang, H, Back, SH, Han, SB & Cho, S 2014, 'Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines', Oncotarget, vol. 5, no. 18, pp. 8515-8527.
Kang H, Song J, Choi K, Kim H, Choi M, Lee SY et al. Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines. Oncotarget. 2014 Jan 1;5(18):8515-8527.
Kang, Hyunju ; Song, Jaehyung ; Choi, Kwangman ; Kim, Hyeongki ; Choi, Miri ; Lee, So Young ; Kim, Chonsaeng ; Lee, Sang Jun ; Song, Moon Jung ; Kang, Hyojeung ; Back, Sung Hoon ; Han, Sang Bae ; Cho, Sungchan. / Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines. In: Oncotarget. 2014 ; Vol. 5, No. 18. pp. 8515-8527.
@article{33ab733ec65444cbb3a9b693e39acf9e,
title = "Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines",
abstract = "Lytic induction of latent Kaposi's sarcoma-associated herpesvirus (KSHV) has been considered as a therapeutic option for efficient treatment of several KSHV-associated malignancies. Here, we developed a robust high-throughput screening system that allows an easy and quantitative measurement of lytic induction of latent KSHV and discovered three anthracyclines as potent inducers from screen of FDA-approved drugs. Lytic induction of latent KSHV by three compounds was verified by the significant induction of lytic genes and subsequent production of infectious KSHV. Importantly, lytic induction by three compounds was much more efficient than that by sodium butyrate, a well-characterized inducer of KSHV lytic cycle. Mechanistically, the anthracyclines caused lytic induction of KSHV through apoptosis induced by their DNA intercalation rather than topoisomerase II inhibition. Consequently, our results clearly demonstrated a role of anthracyclines as effective lytic inducers of KSHV and also provided a molecular basis of their use for efficient treatment of diseases associated with KSHV infection.",
keywords = "Anthracyclines, Apoptosis, DNA intercalation, Kaposi's sarcoma-associated herpesvirus (KSHV), Lytic induction",
author = "Hyunju Kang and Jaehyung Song and Kwangman Choi and Hyeongki Kim and Miri Choi and Lee, {So Young} and Chonsaeng Kim and Lee, {Sang Jun} and Song, {Moon Jung} and Hyojeung Kang and Back, {Sung Hoon} and Han, {Sang Bae} and Sungchan Cho",
year = "2014",
month = "1",
day = "1",
language = "English",
volume = "5",
pages = "8515--8527",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "18",

}

TY - JOUR

T1 - Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines

AU - Kang, Hyunju

AU - Song, Jaehyung

AU - Choi, Kwangman

AU - Kim, Hyeongki

AU - Choi, Miri

AU - Lee, So Young

AU - Kim, Chonsaeng

AU - Lee, Sang Jun

AU - Song, Moon Jung

AU - Kang, Hyojeung

AU - Back, Sung Hoon

AU - Han, Sang Bae

AU - Cho, Sungchan

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Lytic induction of latent Kaposi's sarcoma-associated herpesvirus (KSHV) has been considered as a therapeutic option for efficient treatment of several KSHV-associated malignancies. Here, we developed a robust high-throughput screening system that allows an easy and quantitative measurement of lytic induction of latent KSHV and discovered three anthracyclines as potent inducers from screen of FDA-approved drugs. Lytic induction of latent KSHV by three compounds was verified by the significant induction of lytic genes and subsequent production of infectious KSHV. Importantly, lytic induction by three compounds was much more efficient than that by sodium butyrate, a well-characterized inducer of KSHV lytic cycle. Mechanistically, the anthracyclines caused lytic induction of KSHV through apoptosis induced by their DNA intercalation rather than topoisomerase II inhibition. Consequently, our results clearly demonstrated a role of anthracyclines as effective lytic inducers of KSHV and also provided a molecular basis of their use for efficient treatment of diseases associated with KSHV infection.

AB - Lytic induction of latent Kaposi's sarcoma-associated herpesvirus (KSHV) has been considered as a therapeutic option for efficient treatment of several KSHV-associated malignancies. Here, we developed a robust high-throughput screening system that allows an easy and quantitative measurement of lytic induction of latent KSHV and discovered three anthracyclines as potent inducers from screen of FDA-approved drugs. Lytic induction of latent KSHV by three compounds was verified by the significant induction of lytic genes and subsequent production of infectious KSHV. Importantly, lytic induction by three compounds was much more efficient than that by sodium butyrate, a well-characterized inducer of KSHV lytic cycle. Mechanistically, the anthracyclines caused lytic induction of KSHV through apoptosis induced by their DNA intercalation rather than topoisomerase II inhibition. Consequently, our results clearly demonstrated a role of anthracyclines as effective lytic inducers of KSHV and also provided a molecular basis of their use for efficient treatment of diseases associated with KSHV infection.

KW - Anthracyclines

KW - Apoptosis

KW - DNA intercalation

KW - Kaposi's sarcoma-associated herpesvirus (KSHV)

KW - Lytic induction

UR - http://www.scopus.com/inward/record.url?scp=84908006507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908006507&partnerID=8YFLogxK

M3 - Article

C2 - 25237786

AN - SCOPUS:84908006507

VL - 5

SP - 8515

EP - 8527

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 18

ER -