TY - JOUR JF - انستیتو-پاستور-ایران JO - IBJ VL - 8 IS - 1 PY - 2004 Y1 - 2004/1/01 TI - Cytotoxicity Effect of Cladribine on the MCF-7 Human Breast Cancer Cell Line TT - بررسی سیتوتوکسیسیتی کلادربین در رده سلولی سرطان پستان MCF-7 N2 - 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 SP - 7 EP - 12 AU - Hashemi, Mohammad AU - Karami-Tehrani, Fatemeh AU - Ghavami, Saeed AD - KW - Cladribine KW - Apoptosis KW - MCF-7 KW - Caspase-3 KW - Caspase-9 UR - http://ibj.pasteur.ac.ir/article-1-505-en.html ER -