Metal complexes of ursodeoxycholic acid and its metal complexes as potential antitumor agents against colon cancer

Abstract

Colorectal cancer (CRC) takes the third place among the most commonly diagnosed cancer in males and the sec­ond in females. It is the second leading cause of death among neoplastic diseases worldwide. The physiological role of bile acids (BAs) is well known. The prevalence and clinical application of ursodeoxycho­lic acid (UDCA) as well as the data on participation of BAs in the pathogenesis of several liver diseases and gas­trointestinal (colon) tumorigenesis provoke interest in the relationship between UDCA and cancer. Experimen­tal evidence (in vitro and animal studies) suggests that ursodeoxycholic acid may have chemopreventive actions in colorectal cancer. The aim of our study was to evaluate the influence of Cu(II), Zn(II) and Ni(II) complexes of ursodeoxycholic ac­ids on viability and proliferation of cultured human colon cancer cells. In our investigations, we used the permanent cell line HT29 (human colorectal carcinoma) as a model system. The compounds tested were applied at concentrations of 10-200 I¼g/mL for 24-96 h (for short-term experiments with monolayer cell cultures) and 30 days (for long-term experiments with 3D cell colonies) and their effect on cell viability and proliferation was evaluated by the MTT test, neutral red uptake cytotoxicity assay, crystal violet staining, trypan blue dye exclusion technique, double staining with acridine orange and propidium iodide and colony-forming method. Our results showed that the compounds investigated decreased viability and proliferation of the treated cells in a time- and concentration-dependent manner. Metal complexes expressed more pronounced cytotoxic/cytostatic activity compared to the corresponding ligand ursodeoxycholic acid. The metal complexes examined exhibited promising cytotoxic/antiproliferative properties against HT29 colon cancer cells and deserve further studies to clarify better their anti-tumor potential. Acknowledgements: This study was funded by Grant DFNP-17-89/28.07.2017 from the Program `Support of Young Scientists at the Bulgarian Academy of Sciences` and by a mutual project between the Bulgarian Academy of Sciences and the Romanian Academy.