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Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma

Hassler, Melanie R. ; Klisaroska, Aleksandra ; Kollmann, Karoline ; Steiner, Irene ; Bilban, Martin ; Schiefer, Ana-Iris ; Sexl, Veronika ; Egger, Gerda

Biochimie, 2012-11, Vol.94 (11), p.2297-2307 [Periódico revisado por pares]

France: Elsevier B.V

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Título:
Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma
Autor: Hassler, Melanie R. ; Klisaroska, Aleksandra ; Kollmann, Karoline ; Steiner, Irene ; Bilban, Martin ; Schiefer, Ana-Iris ; Sexl, Veronika ; Egger, Gerda
Assuntos: 5-Aza-2′-deoxycytidine ; Anaplastic large cell lymphoma ; Animals ; Antineoplastic Agents - pharmacology ; Azacitidine - analogs & derivatives ; Azacitidine - pharmacology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Decitabine ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases - antagonists & inhibitors ; DNA (Cytosine-5-)-Methyltransferases - metabolism ; DNA Methylation - drug effects ; DNA methyltransferase inhibitor ; Enzyme Inhibitors - pharmacology ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Lymphoma, Large-Cell, Anaplastic - enzymology ; Lymphoma, Large-Cell, Anaplastic - genetics ; Lymphoma, Large-Cell, Anaplastic - metabolism ; Lymphoma, Large-Cell, Anaplastic - pathology ; Mice ; NPM-ALK ; Receptor Protein-Tyrosine Kinases - metabolism ; Research Paper ; T-cell lymphoma ; Transcriptome - drug effects ; Xenograft Model Antitumor Assays
É parte de: Biochimie, 2012-11, Vol.94 (11), p.2297-2307
Descrição: DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16INK4A after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. ► The DNMT inhibitor 5-aza-CdR inhibits growth of ALCL in vitro and in vivo. ► The tumor suppressor p16INK4A is reactivated after treatment. ► Cellular senescence is induced after 5-aza-CdR administration in vitro. ► Genes related to apoptosis, immune response and cell adhesion are main targets.
Editor: France: Elsevier B.V
Idioma: Inglês

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Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma

Hassler, Melanie R. ; Klisaroska, Aleksandra ; Kollmann, Karoline ; Steiner, Irene ; Bilban, Martin ; Schiefer, Ana-Iris ; Sexl, Veronika ; Egger, Gerda

France: Elsevier B.V

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