We investigated the cytotoxic interactions of romidepsin, a histone deacetylase inhibitor, and lenalidomide, an immunomodulatory agent, in a T-cell lymphoma preclinical model. Hut-78 and Karpas-299 cells were treated with romidepsin and lenalidomide alone and in combination. The interaction between romidepsin and lenalidomide was evaluated by the Chou–Talalay method, and cell viability and clonogenicity were also evaluated. Apoptosis, reactive oxygen species (ROS) levels, and cell cycle distribution were determined by flow cytometry. ER stress, caspase activation, and the AKT, MAPK/ERK, and STAT-3 pathways were analyzed by Western blot. Combination treatment with romidepsin and lenalidomide had a synergistic effect in Hut-78 cells and an additive effect in Karpas-299 cells at 24 hours and did not decrease the viability of normal peripheral blood mononuclear cells. This drug combination induced apoptosis, increased ROS production, and activated caspase-8, −9, −3 and PARP. Apoptosis was associated with increased hallmarks of ER stress and activation of UPR sensors and was mediated by dephosphorylation of the AKT, MAPK/ERK, and STAT3 pathways.The combination of romidepsin and lenalidomide shows promise as a possible treatment for T-cell lymphoma. This work provides a basis for further studies.

The histone deacetylase inhibitor romidepsin synergizes with lenalidomide and enhances tumor cell death in T-cell lymphoma cell lines / Cosenza, Maria; Civallero, Monica; Fiorcari, Stefania; Pozzi, Samantha; Marcheselli, Luigi; Bari, Alessia; Ferri, Paola; Sacchi, Stefano. - In: CANCER BIOLOGY & THERAPY. - ISSN 1538-4047. - ELETTRONICO. - 17:10(2016), pp. 1094-1106. [10.1080/15384047.2016.1219820]

The histone deacetylase inhibitor romidepsin synergizes with lenalidomide and enhances tumor cell death in T-cell lymphoma cell lines

COSENZA, Maria;CIVALLERO, Monica;FIORCARI, STEFANIA;POZZI, Samantha;MARCHESELLI, Luigi;BARI, Alessia;FERRI, Paola;SACCHI, Stefano
2016

Abstract

We investigated the cytotoxic interactions of romidepsin, a histone deacetylase inhibitor, and lenalidomide, an immunomodulatory agent, in a T-cell lymphoma preclinical model. Hut-78 and Karpas-299 cells were treated with romidepsin and lenalidomide alone and in combination. The interaction between romidepsin and lenalidomide was evaluated by the Chou–Talalay method, and cell viability and clonogenicity were also evaluated. Apoptosis, reactive oxygen species (ROS) levels, and cell cycle distribution were determined by flow cytometry. ER stress, caspase activation, and the AKT, MAPK/ERK, and STAT-3 pathways were analyzed by Western blot. Combination treatment with romidepsin and lenalidomide had a synergistic effect in Hut-78 cells and an additive effect in Karpas-299 cells at 24 hours and did not decrease the viability of normal peripheral blood mononuclear cells. This drug combination induced apoptosis, increased ROS production, and activated caspase-8, −9, −3 and PARP. Apoptosis was associated with increased hallmarks of ER stress and activation of UPR sensors and was mediated by dephosphorylation of the AKT, MAPK/ERK, and STAT3 pathways.The combination of romidepsin and lenalidomide shows promise as a possible treatment for T-cell lymphoma. This work provides a basis for further studies.
22-set-2016
17
10
1094
1106
The histone deacetylase inhibitor romidepsin synergizes with lenalidomide and enhances tumor cell death in T-cell lymphoma cell lines / Cosenza, Maria; Civallero, Monica; Fiorcari, Stefania; Pozzi, Samantha; Marcheselli, Luigi; Bari, Alessia; Ferri, Paola; Sacchi, Stefano. - In: CANCER BIOLOGY & THERAPY. - ISSN 1538-4047. - ELETTRONICO. - 17:10(2016), pp. 1094-1106. [10.1080/15384047.2016.1219820]
Cosenza, Maria; Civallero, Monica; Fiorcari, Stefania; Pozzi, Samantha; Marcheselli, Luigi; Bari, Alessia; Ferri, Paola; Sacchi, Stefano
File in questo prodotto:
File Dimensione Formato  
The histone deacetylase inhibitor romidepsin synergizes with lenalidomide and enhances tumor cell death in T-cell lymphoma cell lines.pdf

accesso aperto

Descrizione: Articolo principale
Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 1.43 MB
Formato Adobe PDF
1.43 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1113503
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 12
social impact