title: αIIbβ3-integrin Ligands: Abciximab and Eptifibatide as Proapoptotic Factors in MCF-7 Human Breast Cancer Cells.
abstract: Integrin receptors are considered to be the key factors in carcinogenesis. αIIbβ3-Integrin (GP IIb/IIIa) is the main glycoprotein of the surface of platelets, its presence has also been noted on the certain cancer cell lines. The molecular mechanism of its action in cancer cells remains unknown. This study presents effects of two αIIbβ3-inhibitors: Abciximab and Eptifibatide on apoptosis, expression of proline oxidase (POX), signaling molecules ERK 1/2, transcription factor NF-κB and HIF-1α, vascular endothelial growth factor (VEGF) as well as DNA biosynthesis, collagen biosynthesis and prolidase activity in MCF-7 breast cancer cells. Both ligands induced apoptosis, however we found significant differences in molecular mechanism of action between tested αIIbβ3-inhibitors. These differences include expression of POX, HIF-1α, NF-κB,VEGF and collagen biosynthesis. Eptifibatide presented stronger proapoptotic activity in MCF-7 cells than Abciximab. Results of this study suggest that Eptifibatide may be considered as a novel candidate for development of new anticancer therapy.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kononczuk
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Surazynski
authors.forename: Urszula
authors.initials: U
authors.lastname: Czyzewska
authors.forename: Izabela
authors.initials: I
authors.lastname: Prokop
authors.forename: Michal
authors.initials: M
authors.lastname: Tomczyk
authors.forename: Jerzy
authors.initials: J
authors.lastname: Palka
authors.affiliation: Department of Pharmaceutical Analysis, Medical University in Bialystok, ul. Adama Mickiewicza 2D, 15-222 Bialystok, Poland. wmiltyk@umb.edu.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Miltyk
mesh_terms: D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077542:Eptifibatide; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D008024:Ligands; D061986:MCF-7 Cells; D010455:Peptides / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077542:Eptifibatide; D000077284:Abciximab