Cytotoxicity effect of cladribine on the MCF-7 human breast cancer cell line
IBJ-Iranian Biomedical Journal. 2004; 8 (1): 7-12
in English
| IMEMR
| ID: emr-65989
ABSTRACT
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 micro M] has an apoptotic effect on MCF-7 cells and that its intracellular phosphorylation is necessary
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Index:
IMEMR (Eastern Mediterranean)
Main subject:
Breast Neoplasms
/
Tumor Cells, Cultured
/
Cell Line
/
Apoptosis
/
Antineoplastic Agents
Language:
English
Journal:
Iran. Biomed. J.
Year:
2004
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