Objective: 

The polyether ionophore Monensin is a natural antibiotic, applied in veterinary medicine as coccidiostatic and antibacterial agent. Recent data have revealed that Monensin expresses also antitumor activity against cell lines from various malignancies including leukemia, lymphoma, myeloma, renal cell carcinoma and cancers of the colon, breast and cervix. The aim of our study was to evaluate the putative antineoplastic properties of metal complexes of Monensic acid (MonH) - [M(Mon)2(H2O)2] (M = Mg, Ca, Mn, Co, Ni, Zn).

Methods: 

The following model systems were used in our experiments: cultured human permanent cell lines established from glioblastoma multiforme (8MGBA) and cancers of the lung (A549), breast (MCF-7), uterine cervix (HeLa), liver (HepG2) and skin (A431); virus-transformed chicken and rat tumor cells expressing v-myc or v-src oncogene, respectively; primary cultures of chemically induced liver cancer of Zajdela in rat. The investigations were carried out by MTT test, neutral red uptake cytotoxicity assay, crystal violet staining, trypan blue dye exclusion technique, method of Bradford and colony forming method. The ability of the compounds to induce double stranded DNA damages was examined by Comet assay. Double staining with acridine orange and propidium iodide was applied to demonstrate the presence of cytopathological changes.

Results: 

The results obtained reveal that applied at concentrations of 0.5–25 microg/mL for 24–72 h the examined compounds decreased significantly the viability and proliferation of the treated cells in a time- and concentration-dependent manner.

Conclusions: 

These metal(II) complexes have been found to exhibit higher cytotoxic and cytostatic activities as compared to the non-coordinated Monensic acid. Acknowledgement: Supported by Grant DO-02-84/2008, National Science Fund, Bulgaria.