Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders

Takahiro Watanabe, Yoshitaka Sato, H. M.Abdullah Al Masud, Masahiro Takayama, Hiroki Matsuda, Yuya Hara, Yusuke Yanagi, Masahiro Yoshida, Fumi Goshima, Takayuki Murata, Hiroshi Kimura

Research output: Contribution to journalArticle

Abstract

Epstein-Barr virus (EBV) is a well-established tumor virus that has been implicated in a wide range of immunodeficiency-associated lymphoproliferative disorders (LPDs). Although rituximab, a CD20 mAb, has proven effective against EBV-associated LPDs, prolonged use of this drug could lead to resistance due to the selective expansion of CD20 cells. We have previously shown that cyclin-dependent kinase (CDK) inhibitors are able to specifically suppress the expression of viral late genes, particularly those encoding structural proteins; however, the therapeutic effect of CDK inhibitors against EBV-associated LPDs is not clear. In this study, we examined whether CDK inhibitors confer a therapeutic effect against LPDs in vivo. Treatment with alsterpaullone, an inhibitor of the CDK2 complex, resulted in a survival benefit and suppressed tumor invasion in a mouse model of LPDs. Inhibition of CDK efficiently induced G1 cell cycle arrest and apoptosis in EBV-positive B cells. These results suggest that alsterpaullone suppresses cell cycle progression, resulting in the antitumor effect observed in vivo.

Original languageEnglish
Pages (from-to)279-287
Number of pages9
JournalCancer science
Volume111
Issue number1
DOIs
Publication statusPublished - 01-01-2020

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Lymphoproliferative Disorders
Cyclin-Dependent Kinases
Human Herpesvirus 4
Therapeutic Uses
G1 Phase Cell Cycle Checkpoints
Oncogenic Viruses
Viral Genes
Cell Cycle
B-Lymphocytes
alsterpaullone
Apoptosis
Pharmaceutical Preparations
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Watanabe, T., Sato, Y., Masud, H. M. A. A., Takayama, M., Matsuda, H., Hara, Y., ... Kimura, H. (2020). Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders. Cancer science, 111(1), 279-287. https://doi.org/10.1111/cas.14241
Watanabe, Takahiro ; Sato, Yoshitaka ; Masud, H. M.Abdullah Al ; Takayama, Masahiro ; Matsuda, Hiroki ; Hara, Yuya ; Yanagi, Yusuke ; Yoshida, Masahiro ; Goshima, Fumi ; Murata, Takayuki ; Kimura, Hiroshi. / Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders. In: Cancer science. 2020 ; Vol. 111, No. 1. pp. 279-287.
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Watanabe, T, Sato, Y, Masud, HMAA, Takayama, M, Matsuda, H, Hara, Y, Yanagi, Y, Yoshida, M, Goshima, F, Murata, T & Kimura, H 2020, 'Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders', Cancer science, vol. 111, no. 1, pp. 279-287. https://doi.org/10.1111/cas.14241

Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders. / Watanabe, Takahiro; Sato, Yoshitaka; Masud, H. M.Abdullah Al; Takayama, Masahiro; Matsuda, Hiroki; Hara, Yuya; Yanagi, Yusuke; Yoshida, Masahiro; Goshima, Fumi; Murata, Takayuki; Kimura, Hiroshi.

In: Cancer science, Vol. 111, No. 1, 01.01.2020, p. 279-287.

Research output: Contribution to journalArticle

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AU - Takayama, Masahiro

AU - Matsuda, Hiroki

AU - Hara, Yuya

AU - Yanagi, Yusuke

AU - Yoshida, Masahiro

AU - Goshima, Fumi

AU - Murata, Takayuki

AU - Kimura, Hiroshi

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