Ellipticine induces apoptosis in T-cell lymphoma via oxidative 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 (^G245Sp53) and Hut-78 (^R196Stopp53). Ellipticine caused apoptosis in MyLa2000 and SeAx and restored the transcriptional activity of ^G245Sp53 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.

Keywords::

• Ellipticine
• cutaneous T-cell lymphoma
• p53
• DNA damage
• apoptosis

Acknowledgements

The authors are grateful to Mrs Vibeke Pless and Mr Omid Niazi for their excellent technical support with the experiments.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.