Cytotoxic activity and apoptosis induction by a series Ag(I)-NHC complexes on human breast cancer cells and non-tumorigenic epithelial cell line

Abstract

The main problems encountered in treatment with anticancer drugs, undesired side effects, and toxicity. One of the most important parameters in cell transport is the lipophilic and solubility property of the drug. Enough with the potential effects, side effects with minimal demand for new anticancer compounds, mechanisms of action of the compound can meet because of increased efforts to be clarified. In this case, scientists were encouraged to do new research. In particular, the organometallic compounds are one of the topics focused lately. Ag(I)-NHC complexes are one of the most important classes of organometallic compounds. Although the anticancer activity of Ag(I)-NHC complexes have been known recently times, the anticancer effects of 2-morpholino ethyl substituted benzimidazolium derivative, lipophilic, and solubility properties. Ag(I)-NHC complexes have not unknown yet. Therefore, we aimed to investigate of cytotoxic effect and apoptosis mechanism on breast cancer cell lines (MCF7), breast adenocarcinoma cell lines (MDA-MB-231), and non-tumorigenic epithelium cell lines (MCF 10A) of new Ag(I)-NHC complexes that derivative from morpholine-linked benzimidazole, were synthesized and antimicrobial activity was determined in our previous study. The cytotoxicity was determined by the MTS method, and the apoptosis mechanisms were determined the cell cycle, Annexin V, and caspase-3 analysis. A new benzimidazolium salt bearing morpholino ethyl substituent (2) was synthesized. This benzimidazolium salt was characterized by NMR and FT-IR spectroscopic method and elemental analysis technique. Also, the structure of the new benzimidazolium salt was confirmed by single-crystal X-ray diffraction. Ag(I)-NHC complexes inhibited the growth of MCF7 and MDA-MB-231 cells depending on the dosage and time. The complexes 3a and 3b exhibited a significant difference p < 0.05; p < 0.001; and p < 0.001 level depend on depending on the increase in concentration on cancer cells. All compound induced by apoptosis was associated with stopping the cell cycle in phase G1 and the caspase-3 activity exhibited. The complex 3c was the lowest number of caspase-activating cells (2.1%) compared with both the control and other complexes in MDA-MB-231 cells. But the complex 3a was the highest number of caspase-activating cells (% 9.6). These findings have shown that these new Ag(I)-NHC complexes can be important new anticancer agents for breast cancer treatments.