RRC ID 60703
Author Watanabe T, Sato Y, Masud HMAA, Takayama M, Matsuda H, Hara Y, Yanagi Y, Yoshida M, Goshima F, Murata T, Kimura H.
Title Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders.
Journal Cancer Sci
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.
Volume 111(1)
Pages 279-287
Published 2020-1-1
DOI 10.1111/cas.14241
PMID 31743514
PMC PMC6942432
MeSH Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects Benzazepines / pharmacology* Cell Cycle Checkpoints / drug effects Cell Line Cyclin-Dependent Kinase 2 / antagonists & inhibitors Epstein-Barr Virus Infections / drug therapy Epstein-Barr Virus Infections / genetics Epstein-Barr Virus Infections / virology G1 Phase / drug effects HEK293 Cells Herpesvirus 4, Human / pathogenicity* Humans Indoles / pharmacology* Lymphoproliferative Disorders / drug therapy* Lymphoproliferative Disorders / genetics Lymphoproliferative Disorders / virology* Mice Mice, Inbred NOD Protein Kinase Inhibitors / pharmacology*
IF 4.966
Times Cited 0
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