P7.05 - Metal complexes of Meloxicam and Isoxicam decrease viability and proliferation of virus-transformed cancer cells

Abstract

ABSTRACT Introduction: There is growing evidence supporting the potential antitumor properties of non-steroidal anti-inflammatory drugs (NSAIDs). They are among the most consumed drugs over the world, including patients with cancer - a fact which further enhances the interest in the influence of these preparations on the survival and proliferative activity of tumor cells. It is assumed that for the realization of their biological activity is important linking to metal ions in the body. The aim of our study was to evaluate the effect of metal (CuII, ZnII, CoII, NiII) complexes of selective (Meloxicam) and non-selective (Isoxicam) NSAIDs on viability and proliferation of virus-transformed cancer cells. Materials and Methods: Permanent cell lines established from transplantable tumors in chicken (LSCC-SF-Mc29 –E7 - liver cancer, induced by the myelocytomatosis retrovirus Mc29) and rat (LSR-SF-SR–sarcoma, induced by RSV strain Schmidt-Rupin) were used as model systems. The investigations were performed by MTT test, neutral red uptake cytotoxicity assay, crystal violet staining, double-staining with acridine orange and propidium iodide, colony forming method and FACS analysis. The compounds were applied at a concentration range of 10-500 µg/ml for 24-120 h (short-term assays with monolayer cultures) and 18 days (long-term assay with 3D colonies). Results: The compounds examined decrease significantly viability and proliferation of treated cells as well as their ability to grow in semisolid medium in a time- and concentration-dependant manner. Cytopathological changes (including chromatin fragmentation and apoptotic bodies) and lower percentage of cells in G2 / M phase were also found. Conclusions: Cu(II) complexes with Meloxicam and Isoxicam are found to be the most active cytotoxic and cytostatic agents. They are highly effective against LSCC-SF-Mc29 cells that contain v-myc gene – disregulation of its cellular analogues is involved in pathogenesis of > 80% of human cancers. Applied independently, the ligands express lower cytotoxic/cytostatic activity as compared to metal complexes. Acknowledgements: Supported by Grant DFNI - Б 02/30 from 12.12.2014, Bulgaria, and a bilateral project between Bulgarian Academy of Sciences and Romanian Academy