Bcl2-negative MCF7 cells overexpress p53: implications for the cell cycle and sensitivity to cytotoxic drugs

Purpose: Bcl2 is a mitochondrial protein endowed with cytostatic and antiapoptotic activities. In this work we studied the effects of the lack of Bcl2 in MCF7 cells. Methods: The breast cancer cell line MCF7 (Bcl2-positive) and its derivative MCF7/5013 (Bc12-negative) were compared in terms of the level of p53 expression, doubling time and distribution of cells among the cycle phases. Sensitivities to the proapoptotic drugs cisplatinum and staurosporine were measured using a clonogenic assay and the contribution of apoptosis to cytotoxicity was determined with a mitochondrial membrane potential-sensitive dye. Results: Relative to MCF7, MCF7/5013 cells overexpressed p53 and slowly proliferated with a significant accumulation at G(0)/G(1) and depletion in S phase. The cytotoxicity of the DNA-damaging agent cisplatinum was decreased, while that of the protein kinase inhibitor staurosporine was increased. The induced cytotoxicity was essentially due to apoptosis and necrosis, respectively. Conclusions: These results suggest that the lack of Bcl2 accompanied by p53 overexpression affects the distribution of cells among the cell cycle phases and modifies the sensitivity to cytotoxic drugs and the type of cell death.