1. Ellipticine induces apoptosis in T-cell lymphoma via oxidative DNA damage
- Author
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Edyta Biskup, Cecilia Savorani, Robert Gniadecki, and Valentina Manfé
- Subjects
Cancer Research ,Transcription, Genetic ,DNA damage ,Blotting, Western ,alpha-Tocopherol ,Antineoplastic Agents ,Apoptosis ,Biology ,Lymphoma, T-Cell ,Antioxidants ,law.invention ,law ,Cell Line, Tumor ,medicine ,Humans ,T-cell lymphoma ,Ellipticines ,Dose-Response Relationship, Drug ,Molecular Structure ,Cutaneous T-cell lymphoma ,Hematology ,medicine.disease ,G1 Phase Cell Cycle Checkpoints ,Molecular biology ,Lymphoma ,Oncology ,Cell culture ,Mutation ,Cancer research ,Suppressor ,RNA Interference ,Tumor Suppressor Protein p53 ,Cellular model ,DNA Damage - Abstract
The tumor suppressor p53 is often mutated in human cancers. Restoring its antitumor activity has been shown to be a promising therapeutic approach for cancer treatment. Here we analyzed the activity and mechanism of a p53 reactivator, ellipticine, in a cellular model of cutaneous T-cell lymphoma (CTCL), a disease that is progressive, chemoresistant and refractory to treatment. We tested the effect of ellipticine in three cell lines with different p53 status: MyLa2000 (p53(wt/wt)), SeAx ((G245S)p53) and Hut-78 ((R196Stop)p53). Ellipticine caused apoptosis in MyLa2000 and SeAx and restored the transcriptional activity of (G245S)p53 in SeAx. However, p53 siRNA knockdown experiments revealed that p53 was not required for ellipticine-induced apoptosis in CTCL. The lipophilic antioxidant α-tocopherol inhibited ellipticine-dependent apoptosis and we linked the apoptotic response to the oxidative DNA damage. Our results provide evidence that ellipticine-induced apoptosis is exerted through DNA damage and does not require p53 activation in T-cell lymphoma.
- Published
- 2014