The success of cisplatin in antitumour therapy as one of the main chemotherapeutics in clinical practice motivated scientists’ interest in metal compounds. Chemotherapeutics, combining several biologically active subunits in one molecule, can modulate different regulatory pathways in the cell and thus achieve higher efficacy than drugs that affect only one cellular process. That is why the identification and study of new promising molecular structures as potential anticancer drugs is a great challenge. The different results related to the cytotoxic potential of DK-164 and CC-78 associated with the examined cellular mechanisms induced in lung cancer cells might be used to conclude the specific functions of the various functional groups in the ferrocene compounds, which can offer new perspectives for the design of antitumour drugs.Ĭhemotherapy plays a significant role in the treatment of cancer worldwide. In the non-cancerous cells, MRC5, both compounds produced ROS similar to the positive control for the same incubation period. In A549, DK-164 generated oxidative stress close to the positive control after 48 h, while CC-78 had a moderate effect on the cellular redox status. Both compounds caused a significant transfer of the p53 protein in the nucleus of A549 cells but not in non-cancerous MRC5 cells. DK-164 treatment of A549, H1299, and MRC5 cells for 48 h significantly increased the fluorescence signal of the NFkB (nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells) protein in the nucleus in all three cell lines, while CC-78 did not provoke NFkB translocation in any of the tested cell lines. The level of induced autophagy was similar for both substances in cancer cells. DK-164 showed predominantly pro-apoptotic activity in non-small cell lung carcinoma (NSCLC) cells, while CC-78 caused accidental cell death with features characteristic of necrosis. The cytotoxicity of CC-78 toward H1299 was even higher than that of the well-established anticancer drugs cisplatin and tamoxifen, but it did not reveal any noticeable selective effect. DK-164 demonstrated remarkable selectivity toward cancer cells and more pronounced cytotoxicity against A549. Two ferrocene derivatives, DK-164 and CC-78, with different residues were tested for cytotoxic potential on non-small lung cancer cell lines, A549 and H1299, and non-cancerous MRC5. The successful design of antitumour drugs often combines in one molecule different biologically active subunits that can affect various regulatory pathways in the cell and thus achieve higher efficacy.
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