Anticancer activity of silver(I) cyclohexyldiphenylphosphine complexes toward SNO cancer cells

Abstract

Silver and its derivatives have been and are currently used as antimicrobial and antibacterial agents. However, their use is rather limited to date as anticancer agents. Thus, this study focuses on the synthesis and characterization of three silver(I) complexes which have the ability to adopt different geometries, and to induce cancer cell death in SNO esophageal cancer cells. Silver thiocyanate was reacted in different ratios with cyclohexyldiphenylphosphine to obtain 1:1 (complex 1), 1:2 (complex 2), and 1:3 (complex 3) molar ratios of silver(I):cyclohexyldiphenylphosphine complexes. These complexes were characterized using conventional spectroscopic techniques, which included ¹H, ¹³C, and ³¹P NMR, FTIR, and microanalysis (%C, H, N, S). In addition, the single-crystal X-ray structures of complexes 1 and 2 were determined. Moreover, all three complexes displayed toxic activity toward the malignant SNO cells with IC₅₀ concentrations below 5 μM as determined with an alamarBlue® viability assay. Morphological and flow cytometric analyses were included to identify the possible mode of cancer cell death. These biochemical assays revealed that all three treatments induced apoptosis due to the presence of specific apoptotic markers.

Keywords:

• Anticancer agents
• AgSCN
• phosphine ligands
• apoptosis
• SNO cancer cells
• phosphatidylserine externalization

Acknowledgements

We would like to acknowledge Mrs. Z. Mpela from the University of Johannesburg in the Department of Biochemistry for assistance with the anticancer studies. Authors would also like to acknowledge Mr. D. Harris and Dr. R. Meyer (Shimadzu S.A.) for use of their equipment.