:: Volume 8, Issue 1 (1-2004) ::
ibj 2004, 8(1): 7-12 Back to browse issues page
Cytotoxicity Effect of Cladribine on the MCF-7 Human Breast Cancer Cell Line
Mohammad Hashemi , Fatemeh Karami-Tehrani * , Saeed Ghavami
Cladribine, an analogue of deoxyadenosine, is highly toxic for both non-dividing and proliferating cells and has shown activity in the treatment of several malignancies. Therefore, the aim of the present study is to investigate the cytotoxicity effect of cladribine (2-CdA) on the breast cancer cell line, MCF-7 (estrogen receptor positive, ER+). MTT assay, annexin V-Fluorescein/PI and Hoechst 33258 staining were used to detect cytotoxicity and cell apoptosis. The activation of caspase-3 and -9 was assayed using caspase activation assay kits. Gel electrophoresis was performed to detect DNA fragmentation. Treatment of MCF-7 cells with different concentrations of 2-CdA resulted in a significant increase in the cell death. Annexin V-Fluorescein/PI and Hoechst 33258 staining revealed that the cell death was mainly an apoptotic type. A significant (p<0.05) increase in the activity of caspase-9 was observed but Caspase-3 activity was unchanged and DNA laddering profile was not obtained. Pre-treatment of the cells with kinase inhibitor, 5¢-amino-5¢-deoxyadenosine inhibited the cytotoxicity effect of cladribine. In conclusion, this study has shown that high dose of cladribine (higher than 25 μM) has an apoptotic effect on MCF-7 cells and that its intracellular phosphorylation is necessary
Keywords: Cladribine, Apoptosis, MCF-7, Caspase-3, Caspase-9
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Hashemi M, Karami-Tehrani F, Ghavami S. Cytotoxicity Effect of Cladribine on the MCF-7 Human Breast Cancer Cell Line. ibj. 2004; 8 (1) :7-12
URL: http://ibj.pasteur.ac.ir/article-1-505-en.html

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