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Novel HDAC inhibitors exhibit pre-clinical efficacy in lymphoma models and point to the importance of CDKN1A expression levels in mediating their anti-tumor response.
Mensah, Afua Adjeiwaa; Kwee, Ivo; Gaudio, Eugenio; Rinaldi, Andrea; Ponzoni, Maurilio; Cascione, Luciano; Fossati, Gianluca; Stathis, Anastasios; Zucca, Emanuele; Caprini, Gianluca; Bertoni, Francesco.
Afiliação
  • Mensah AA; Lymphoma & Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.
  • Kwee I; Lymphoma & Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.
  • Gaudio E; Dalle Molle Institute for Artificial Intelligence (IDSIA), Manno, Switzerland.
  • Rinaldi A; Lymphoma & Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.
  • Ponzoni M; Lymphoma & Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.
  • Cascione L; Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy.
  • Fossati G; Lymphoma & Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.
  • Stathis A; IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Zucca E; Preclinical R&D Department, Italfarmaco S.p.A., Cinisello Balsamo, Milan, Italy.
  • Caprini G; IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Bertoni F; IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Oncotarget ; 6(7): 5059-71, 2015 Mar 10.
Article em En | MEDLINE | ID: mdl-25671298
We investigated the pre-clinical activities of two novel histone deacetylase inhibitors (HDACi), ITF-A and ITF-B, in a large panel of pre-clinical lymphoma models. The two compounds showed a dose-dependent anti-proliferative activity in the majority of cell lines. Gene expression profiling (GEP) of diffuse large B-cell lymphoma (DLBCL) cells treated with the compounds showed a modulation of genes involved in chromatin structure, cell cycle progression, apoptosis, B-cell signaling, and genes encoding metallothioneins. Cell lines showed differences between the concentrations of ITF-A and ITF-B needed to cause anti-proliferative or cytotoxic activity, and cell cycle and apoptosis genes appeared implicated in determining the type of response. In particular, CDKN1A expression was higher in DLBCL cells that, to undergo apoptosis, required a much higher amount of drug than that necessary to induce only an anti-proliferative effect.In conclusion, the two novel HDACi ITF-A and ITF-B demonstrated anti-proliferative activity across different mature B-cell lymphoma cell lines. Basal CDKN1A levels appeared to be important in determining the gap between HDACi concentrations causing cell cycle arrest and those that lead to cell death.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma Difuso de Grandes Células B / Inibidor de Quinase Dependente de Ciclina p21 / Inibidores de Histona Desacetilases Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma Difuso de Grandes Células B / Inibidor de Quinase Dependente de Ciclina p21 / Inibidores de Histona Desacetilases Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article