Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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αIIbβ3-integrin Ligands: Abciximab and Eptifibatide as Proapoptotic Factors in MCF-7 Human Breast Cancer Cells

Author(s): Joanna Kononczuk, Arkadiusz Surazynski, Urszula Czyzewska, Izabela Prokop, Michal Tomczyk, Jerzy Palka, Wojciech Miltyk.

Graphical Abstract:


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.

Keywords: αIIbβ3-integrins, αIIbβ3-inhibitors, abciximab, eptifibatide, MCF-7 breast cancer cells, apoptosis.

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Article Details

VOLUME: 16
ISSUE: 13
Year: 2015
Page: [1429 - 1437]
Pages: 9
DOI: 10.2174/1389450115666140804220441
Price: $58