Histone deacetylase inhibitor romidepsin induces efficient tumor cell lysis via selective down-regulation of LMP1 and c-myc expression in EBV-positive diffuse large B-cell lymphoma

Cancer Letters
Dong-Yeop ShinSeung-Sook Lee

Abstract

We investigated the role of the histone deacetylase inhibitor, romidepsin, in Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL), an aggressive non-Hodgkin lymphoma with poor clinical outcomes. We used EBV-positive and EBV-negative DLBCL cell lines and generated two EBV-transfected cell lines, LY7/EBV and U2932/EBV. Romidepsin was cytotoxic to cultured EBV-positive cells via the activation of the caspase cascade. Moreover, in vivo mice xenograft models demonstrated the cytotoxicity of romidepsin to EBV-positive DLBCL cells. Romidepsin induced cytotoxicity via the reduction of LMP1 and c-myc expression in EBV-positive cells. Inhibiting either LMP1 or c-myc using small inhibitory RNAs caused partial cytotoxicity in EBV-positive Farage and U2932/EBV lines. The dual inhibition of LMP1 and c-myc showed a synergistic cytotoxic effect in EBV-positive cells similar in magnitude to that of romidepsin alone. In addition, either double blockade of LMP1 and c-myc activity or romidepsin single treatment activated EBV lytic cycle in EBV-positive cells. In conclusion, romidepsin exerts strong anti-tumor activity in EBV-positive DLBCL via the inhibition of both LMP1 and c-myc. Our findings indicate that romidepsin might be...Continue Reading

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Citations

Jan 15, 2016·Virchows Archiv : an International Journal of Pathology·Luisa LorenziFabio Facchetti
Jul 28, 2016·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Hui ZhangJun Li
Apr 27, 2016·The FEBS Journal·Andrea NewboldRicky W Johnstone
Jun 13, 2019·Blood Advances·Carlos Murga-ZamalloaRyan A Wilcox
Jun 3, 2021·Pathogens·Martin A Prusinkiewicz, Joe S Mymryk
Dec 1, 2018·Future Virology·Mujeeb R Cheerathodi, David G Meckes

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