Specific impact of acridine antitumor agents on the survival potency of selected non-cancerous cells: Toxicological insights.

Although anticancer agents are designed to selectively target malignant cells, they often also exhibit considerable nonspecific toxicity toward normal tissues, leading to adverse side effects in patients. In this context, the present study aimed to evaluate the toxic effects of a novel unsymmetrical bisacridine anticancer agent (UA) on normal, noncancerous cells and to compare its activity with that of three established acridine monomers (AMs). To assess the potential side effects of UA in different regions of the human body, four non-tumor cell models were selected: (i) erythrocytes, representing the circulatory system; (ii) MRC-5 cells, derived from normal lung tissue; (iii) CCD 841 CoN cells, originating from normal colon epithelium; and (iv) hTERT-HPNE cells, representing immortalized normal pancreatic epithelial cells. The results demonstrated that, apart from the dimer C-2042, which caused a slight increase in erythrocyte hemolysis and potassium leakage, neither UA nor the acridine monomers induced significant erythrocyte damage, promoted heme iron oxidation, or caused structural alterations in hemoglobin. In the remaining non-tumor cell models, UA and the three acridine monomers exhibited measurable cytotoxicity, with the cytotoxicity of UA falling between the levels observed for the monomers. Importantly, the cytotoxicity of all tested compounds toward non-tumor cells was several times lower than that previously observed in cancer cells derived from the corresponding tissues. Taken together, these findings indicate that UA exhibits limited toxicity toward normal, noncancerous cells, supporting its potential as an effective and safer anticancer agent.