Paper Title
Down-Regulation Of Pma-Induced Gelatinase B Production By A Selective Β1 Receptor Blocker In Leukemic Cells In Vitro

Abstract
Background: Metoprolol has been largely used in treatment of cardiovascular diseases. Moreover, anti-cancer effects of metoprolol have been demonstrated. Matrix metalloproteinases (MMPs), as a large group of enzymes, are involved in numerous pathological disorders including tumor progression and invasion. Gelatinase B (MMP-9) plays an essential role in cancer pathogenesis and metastasis. In this study effect of metoprolol on gelatinase B production in leukemic U937 and Molt-4 cells has been assessed in vitro. Materials and Methods: Human U937 and Molt-4 leukemic cells were separately cultured in complete RPMI-1640 medium. Then the cells at exponential growth phase were stimulated with phorbol 12-myristate 13-acetate (PMA) at optimum dose and next treated with different concentrations of metoprolol (1-1000 μg/ml) for 24 hours. The level of gelatinase B in culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA). Results: Metoprolol significantly decreased the PMA- stimulated gelatinase B production in both U937 and Molt-4 cells dose-dependently. Conclusion: Metoprolol could be a potential gelatinase B inhibitor. As gelatinase B plays a vital role in tumor expansion and metastasis, anti-tumor effect of metoprolol might be partly due to its suppressive effects on gelatinase B secretion. So metoprolol may be useful as a novel therapeutic candidate for cancers such as leukemia in which gelatinase B is over-expressed. Key words: Metoprolol, Leukemia, Gelatinase B