title: The combined treatment with novel platinum(II) complex and anti-MUC1 increases apoptotic response in MDA-MB-231 breast cancer cells.
abstract: 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.
authors.affiliation: Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland. agnieszka.gornowicz@umb.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gornowicz
authors.affiliation: Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bielawska
authors.affiliation: Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Czarnomysy
authors.affiliation: Deparment of Medical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland.
authors.forename: Halina
authors.initials: H
authors.lastname: Gabryel-Porowska
authors.affiliation: Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Muszyńska
authors.affiliation: Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089, Białystok, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bielawski
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods*; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018396:Mucin-1 / Q000276:immunology*; D009944:Organoplatinum Compounds / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; C060192:MUC1 protein, human; D018396:Mucin-1; D009944:Organoplatinum Compounds
keywords: Anti-MUC1; Anticancer drugs; Apoptotic markers; Platinum complexes; Targeted therapy