PMID- 26112902 OWN - NLM STAT- MEDLINE DCOM- 20160706 LR - 20210426 IS - 1573-4919 (Electronic) IS - 0300-8177 (Print) IS - 0300-8177 (Linking) VI - 408 IP - 1-2 DP - 2015 Oct TI - The combined treatment with novel platinum(II) complex and anti-MUC1 increases apoptotic response in MDA-MB-231 breast cancer cells. PG - 103-13 LID - 10.1007/s11010-015-2486-z [doi] AB - 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. FAU - Gornowicz, Agnieszka AU - Gornowicz A AD - Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089, Bialystok, Poland. agnieszka.gornowicz@umb.edu.pl. FAU - Bielawska, Anna AU - Bielawska A AD - Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089, Bialystok, Poland. FAU - Czarnomysy, Robert AU - Czarnomysy R AD - Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Bialystok, Poland. FAU - Gabryel-Porowska, Halina AU - Gabryel-Porowska H AD - Deparment of Medical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089, Bialystok, Poland. FAU - Muszynska, Anna AU - Muszynska A AD - Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Bialystok, Poland. FAU - Bielawski, Krzysztof AU - Bielawski K AD - Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Bialystok, Poland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150627 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Antibodies, Monoclonal) RN - 0 (MUC1 protein, human) RN - 0 (Mucin-1) RN - 0 (Organoplatinum Compounds) SB - IM MH - Antibodies, Monoclonal/*pharmacology MH - Apoptosis MH - Breast Neoplasms/*drug therapy/immunology MH - Cell Line, Tumor MH - Combined Modality Therapy/*methods MH - DNA Fragmentation/drug effects MH - Female MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - Membrane Potential, Mitochondrial/drug effects MH - Mucin-1/*immunology MH - Organoplatinum Compounds/*pharmacology PMC - PMC4768227 OTO - NOTNLM OT - Anti-MUC1 OT - Anticancer drugs OT - Apoptotic markers OT - Platinum complexes OT - Targeted therapy EDAT- 2015/06/27 06:00 MHDA- 2016/07/07 06:00 PMCR- 2015/06/27 CRDT- 2015/06/27 06:00 PHST- 2015/01/20 00:00 [received] PHST- 2015/06/18 00:00 [accepted] PHST- 2015/06/27 06:00 [entrez] PHST- 2015/06/27 06:00 [pubmed] PHST- 2016/07/07 06:00 [medline] PHST- 2015/06/27 00:00 [pmc-release] AID - 10.1007/s11010-015-2486-z [pii] AID - 2486 [pii] AID - 10.1007/s11010-015-2486-z [doi] PST - ppublish SO - Mol Cell Biochem. 2015 Oct;408(1-2):103-13. doi: 10.1007/s11010-015-2486-z. Epub 2015 Jun 27.