Metals have been used in the treatment of various diseases since ancient times. The discovery of cisplatin in 1960 - one of the most effective and widely used drugs in current clinical oncology, opened a new page in medical chemistry and stimulated scientists to search for new metal compounds with promising antitumor activity and acceptable tolerance.
The aim of our study was to evaluate the influence of Zn(II), Co(II) and Ni(II) complexes with kojic acid on viability and proliferation of human cancer (HeLa uterine cervical carcinoma) and non-cancer (Lep-3 embryonic fibroblasts) cells. The investigations were based on short-term (up to 72 h, with monolayer cultures) and long-term (up to 40 days, with 3D cancer cell colonies) experiments using methods with different cellular/molecular targets and mechanisms of action: MTT test, neutral red uptake cytotoxicity assay, crystal-violet staining, double staining with acridine orange and propidium iodide, Annexin V/FITC assay and colony-forming method. The results obtained revealed that: i) applied at a concentration range of 5 - 200 μg/mL the compounds tested decrease the percent of the viable treated cells (as compared to the control) in a time- and concentration-dependent manner; ii) administered at a concentration of 200 μg/ml the complexes completely inhibit the ability of HeLa uterine cervical carcinoma cells to form 3D cell colonies in a semi-solid medium; iii) cancer HeLa cells have been found to be more sensitive to the cytotoxic effect of the compounds examined as compared to the non-cancer Lep-3 fibroblasts; iv) Co(II) complex with kojic acid shows the highest cytotoxic activity among the compounds investigated and has demonstrated to be more effective than cisplatin.
This study was funded by Grant DFNP-17-73/28.07.2017 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.
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