Effects of disulfiram, metal complexes of meloxicam and their combinations on viability and proliferation of human non-small cell lung cancer cells

Abstract

The selective non-steroidal anti-inflammatory drug meloxicam and its metal [Zn(II), Cu(II), Co(II), Ni(II)] complexes were found in our previous investigations to inhibit the in vitro growth of cultured cell lines established from various cancers (virus-induced transplantable chicken hepatoma and rat sarcoma, human cervical carcinoma and glioblastoma multiforme).Disulfiram, used for decades in the treatment of chronic alcoholism, was proved to express also promising antineoplastic properties.The aim of the present study was to evaluate the influence of disulfiram, metal complexes of meloxicam and their combinations on viability and proliferation of human non-small cell lung cancer cells. The permanent cell line A549 reported to express the cyclooxigenase 2, was used as a model system. Disulfiram was applied at concentrations of 03-100 µg/ml; meloxicam and its Zn(II), Cu(II) and Co(II) complexes were administered at a concentration range of 10-500µg/ml. The investigations were performed using MTT test - the golden standard for cytotoxicity assays, neutral red uptake cytotoxicity assay and double staining with acridine orange and propidium iodide. The results obtained revealed that: i) Disulfiram decreased viability and proliferation of the treated cells in a time- and concentration-dependent manner; ii) The percent of viable A549 cells cultured in the presence of meloxicam and its metal complexes was relatively high as compared to the control (CC50 were not determined); iii) The cytotoxic/cytostatic effect of Cu(II) comlex of Meloxicam was significantly increased when combined with Disulfiram (applied at relatively low toxic concentrations of 6.25 and 12.5µg/ml).Acknowledgements: This study was funded by the Program `Support of Young Scientists at the Bulgarian Academy of Sciences` and a bilateral project between Bulgarian Academy of Sciences and Romanian Academy.