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Paper Information

Journal:   IRANIAN BIOMEDICAL JOURNAL   January 2004 , Volume 8 , Number 1; Page(s) 7 To 12.
 
Paper: 

CYTOTOXICITY EFFECT OF CLADRIBINE ON THE MCF-7 HUMAN BREAST CANCER CELL LINE

 
 
Author(s):  HASHEMI M., KARAMI TEHRANI FATEMEH*, GHAVAMI S.
 
* 
 
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 mM) has an apoptotic effect on MCF-7 cells and that its intracellular phosphorylation is necessary.
 
Keyword(s): CLADRIBINE, APOPTOSIS, MCF-7, CASPASE-3, CASPASE-9
 
References: 
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