Abstract 5674: Effect of clofarabine on apoptosis and DNA synthesis in human breast cancer

Abstract

Abstract As a second-generation nucleoside analogue, clofarabine, is employed primarily for the treatment of paediatric patients with relapsed or refractory acute lymphoblastic leukaemia after at least two prior regimens, but its application toward the solid tumors attracts more and more attention recently. In this study, the effect of clofarabine was investigated in several breast cancer cell lines and compared to a normal cell line (hTERT RPE-1). Upon treatment with 0.1 or 0.2μM clofarabine for 48 hrs, inhibition of cell growth (S-phase arrest) was investigated in both breast cancer and normal cell lines. And we observed that the induction of apoptosis was obvious in the all breast cancer cells but not in the normal cells. More than 40% breast cancer cells entered apoptotic or/and necrotic process after they were treated to 0.2μM clofarabine for 48 hrs. This was associated with an increase in dCK activity in malignant cells between 2.2 and 4.7 folds but only 1.2-fold in hTERT RPE-1 cells. Upon treatment with clofarabine, the cleaved-caspase 3 was observed and the level of anti-apoptotic protein (Bcl-2 and Bcl-xL) down-regulated significantly in the breast cancer cell lines, but not in the hTERT RPE-1 cells. In addition, the sensitivity of all breast cancer cells to the toxicity of clofarabine was attenuated significantly by down-regulation of dCK with siRNA. These results showed that as a single-agent and combination regim clofarabine is worth to be explored in solid tumor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5674. doi:1538-7445.AM2012-5674