Discrimination of the Effects of Doxorubicin on Two Different Breast Cancer Cell Lines on Account of Multidrug Resistance and Apoptosis
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey, E-mail: [email protected]
Breast cancer is one of the most common cancer types and malfunctioning proteins in apoptotic pathways are known to be the main contributors of cancer development. In this study MCF-7 and MDA-MB-231 breast cancer cell lines were treated with a potent chemotherapeutic agent, Doxorubicin. IC50 values were calculated to be 8306 and 6602 nM, respectively. Percentage of the cells in cell cycle arrest increased in a dose-dependent manner and was more evident in MDA-MB-231 cells. Apoptotic cell number increased in MCF-7 and Bax/Bcl-2 ratio was measured to be ~ 7 fold higher in cells treated with 200 nM of doxorubicin when compared to the control. Likewise, apoptotic cell rate increased in MDA-MB-231 cells and Bax/Bcl-2 ratio was increased by 2 fold compared to the control. Doxorubicin was also found to suppress Mdr-1 in a concentration-dependent manner and the outcome was more evident in MCF-7 cells. Drug efflux assay results were also shown to be consistent with Mdr-1 gene expression levels in both cell lines. Consequently it was concluded that doxorubicin directly influences apoptotic pathway and multidrug resistance in both MCF-7 and MDA-MB-231 cells even though data all together suggest that the effect is more significant on MDA-MB-231.