P7.04 - Influence of Deoxycholic acid and its metal complexes on viability and proliferation of human tumor cell lines

Abstract

ABSTRACT Introduction: The biological role of bile acids is well known and a number of derivatives of cholic acid are regarded as suitable candidates for the establishment of conjugated agents in carrying out site-directed anti-cancer therapy. At the same time there are data about carcinogenicity of some of these acids, which requires in-depth study of their relationship with cancer cells. The aim of our study was to evaluate the influence of deoxycholic acid (DCA) and its metal (CuII, ZnII, NiII) complexes on viability and proliferation of cultured human tumor cells. Materials and Methods: Human cell lines established from cancers of the breast (MCF-7), uterine cervix (HeLa), lung (A549), liver (HepG2), brain (8MGBA) and colon (HT29) were used as experimental models. A complex approach involving methods with different cellular / molecular targets was applied to evaluate the putative cytotoxic/cytostatic activities of the compounds: MTT test, neutral red uptake cytotoxicity assay, crystal violet staining, double staining with acridine orange and propidium iodide, Comet assay, colony-forming method. Data were processed by statistical analyses. Results: Administered at a concentration range of 10-200 µg/ml for 24–120 h the compounds examined decrease in various degree the viability and proliferation of the treated cells in a time- and concentration dependant manner and suppress their ability to form 3D colonies in semi-solid medium. Cytopathological changes including double stranded DNA damages have also been observed. Conclusions: The compounds investigated reduce significantly the growth of cell lines established from some of the most common and aggressive human cancers. Cu(II) and Zn(II) complexes of DCA are found to express the most promising antitumor activity. Applied independently, DCA is less effective as compared to its metal complexes. Among the cell lines involved as model systems in our study, A549 non-small cell lung cancer cells show the highest sensitivity to the cytotoxic/cytostatic properties of the tested compounds. Acknowledgements: Supported by Grant DFNI-Б02/30 from 12.12.2014 from National Scientific Fund in Bulgaria and a bilateral project between Bulgarian Academy of Sciences and Romanian Academy.