A Comparison of the Toxicity of Mono, Bis, Tris and Tetrakis Phosphino Silver Complexes on SNO Esophageal Cancer Cells

Abstract

Background: A broad range of metal-coordinated complexes have been studied for their anticancer activities. However, some of these complexes display high toxicity profiles to non-malignant cells, therefore limiting their use in cancer therapeutics.

Aims/method: Several silver(I) triphenylphosphine adducts were prepared as 1:1 to 1:4 ratios of silver nitrate to triphenylphosphine. They were further used to determine their anticancer activity in a malignant SNO esophageal cell line. The silver(I) phosphine adducts include: [Ag(PPh3)]NO3 (1); [Ag(PPh3)2]NO3 (2); [Ag(PPh3)3]NO3 (3) and [Ag(PPh3)4]NO3 (4). In addition, the activity of complexes 1-4 was compared to previously reported complexes [Ag(Ph2P(CH2)2PPh2)2]NO3 (5) and [Ag(Ph2P(CH2)3PPh2)2]NO3 (6). The cytotoxicity of complexes 1-6 was also evaluated in non-malignant human dermal fibroblast cells (HDF-a).

Results: The majority of the complexes (specifically those containing PPh3) were found to be highly toxic to the SNO cells and less toxic towards HDF-a cells, as determined by the alamarBlue® assay. Morphological studies and flow cytometry confirmed that the silver(I) complexes induced apoptosis in the malignant cells.

Conclusion: These results may have an impact on research related to drug discovery and silver(I) phosphine complexes could be added to the arsenal of anticancer agents in addition to the silver-bis-diphenylphosphinoethane and silver-bis-diphenylphosphinopropane adducts.

Keywords: Silver(I) phosphine complexes; anticancer activity; apoptosis; cytotoxicity; drug discovery; esophageal cancer..