caa a22 4500 606235221 CHVBK 20210128101241.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s11010-015-2486-z doi (NATIONALLICENCE)springer-10.1007/s11010-015-2486-z The combined treatment with novel platinum(II) complex and anti-MUC1 increases apoptotic response in MDA-MB-231 breast cancer cells [Elektronische Daten] [Agnieszka Gornowicz, Anna Bielawska, Robert Czarnomysy, Halina Gabryel-Porowska, Anna Muszyńska, Krzysztof Bielawski] New strategy of cancer's targeting treatment is combining monoclonal antibodies with chemotherapeutic agents. An important goal of targeted therapy appears to be a transmembrane glycoprotein type I—mucin 1 (MUC1), which is overexpressed in tumors of epithelial origin, especially in breast cancer. The goal of the study was to check the effect of monoclonal antibody against MUC1 with novel platinum(II) complex (Pt12) on selected aspects of apoptosis in human MDA-MB-231 breast cancer cells. The number of apoptotic and necrotic cells was measured using annexin V binding assay. The decrease of mitochondrial membrane potential (MMP) and DNA fragmentation was analyzed. Finally, the influence of novel platinum(II) complex (Pt12) used with anti-MUC1 on the concentration of selected markers of apoptosis such as Bax, caspase-8, -9, and caspase-3 was performed using ELISA. The results from combined treatment were compared with those obtained using monotherapy. In our study, we proved that anti-MUC1 used in combination with Pt12 strongly induced apoptosis in MDA-MB-231 breast cancer cell line. The effect was stronger than treatment with Pt12, cisplatin, anti-MUC1, and anti-MUC1 used with cisplatin. We also observed the highest decrease of MMP and the strongest DNA fragmentation after such a combined treatment. The results obtained from ELISA showed increased concentration of Bax, caspases-8, -9, -3 compared to monotherapy. Our study proved that Pt12 together with anti-MUC1 strongly induced apoptosis in estrogen-negative breast cancer cell line (MDA-MB-231). The apoptosis may go through extrinsic pathway associated with caspase-8 as well as intrinsic pathway connected with caspase-9. The Author(s), 2015 Anti-MUC1 nationallicence Anticancer drugs nationallicence Platinum complexes nationallicence Targeted therapy nationallicence Apoptotic markers nationallicence Gornowicz Agnieszka Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut Bielawska Anna Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut Czarnomysy Robert Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut Gabryel-Porowska Halina Deparment of Medical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut Muszyńska Anna Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut Bielawski Krzysztof Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 103-113 0300-8177 408:1-2<103 2015 408 11010 https://doi.org/10.1007/s11010-015-2486-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2486-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gornowicz Agnieszka Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut NATIONALLICENCE 700 1- Bielawska Anna Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut NATIONALLICENCE 700 1- Czarnomysy Robert Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut NATIONALLICENCE 700 1- Gabryel-Porowska Halina Deparment of Medical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut NATIONALLICENCE 700 1- Muszyńska Anna Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut NATIONALLICENCE 700 1- Bielawski Krzysztof Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 103-113 0300-8177 408:1-2<103 2015 408 11010