The induction of cell death by phosphine silver(I) thiocyanate complexes in SNO-esophageal cancer cells Zelinda Human • Appollinaire Munyaneza • Bernard Omondi • Natasha M. Sanabria • Reinout Meijboom • Marianne J. Cronje ´ Received: 20 October 2014 / Accepted: 21 December 2014 Ó Springer Science+Business Media New York 2014 Abstract Esophageal cancer is one of the least studied cancers and is found to be prominent in black South African males. It is mainly diagnosed in the late stages, and patients tend to have a low 5-year survival rate of only 10 %. Silver is generally used as an antimicrobial agent, with limited reports on anticancer studies. In this study, dimeric silver(I) thiocyanate complexes were used containing a variation of 4-substitued triphenyl- phosphines, including [AgSCN(PPh 3 ) 2 ] 2 (1), [AgSCN {P(4-MeC 6 H 4 ) 3 } 2 ] 2 (2), [AgSCN{P(4-FC 6 H 4 ) 3 } 2 ] 2 (3) and [AgSCN{P(4-ClC 6 H 4 ) 3 } 2 ] 2 (4). All four complexes, with their respective phosphine ligands, PPh 3 (L1), P(4- MeC 6 H 4 ) 3 (L2), P(4-FC 6 H 4 ) 3 (L3) and P(4-ClC 6 H 4 ) 3 (L4), were subjected to in vitro toxicity studies in SNO- esophageal cancer cells, using an alamarBlue Ò assay. Morphological changes, including blebbing and apop- totic body formation, were observed. Phosphatidylserine externalization, a marker of apoptosis, was quantified by flow cytometry. The phosphine ligands L1–L4, on their own, had minimal effect on the malignant while complexes 1–4 resulted in significant cell death. A 109 decreased concentration of these complexes had similar effects than cisplatin, used as the positive control. These complexes show promise as anticancer agents. Keywords Silver(I) thiocyanate complexes Á Phosphines Á Anticancer Á Flow cytometry Á Apoptosis Á SNO-esophageal cancer Introduction The growth abnormalities associated with cancer have developed due to external, e.g. chemicals, infectious microbes, tobacco and radiation, and/or internal agents, e.g. hormones, immune conditions, inherited and metabolic mutations (Garcia et al. 2007). Esoph- ageal cancer has been one of the least studied cancers, in spite of it being responsible for a sixth of all cancer deaths (Pisani et al. 1993). It is identified as a high risk malignancy in South African Black males, especially in the Transkei and Sowetan regions (Jaskiewicz et al. 1987; Sumeruk et al. 1992; Dlamini and Bhoola 2005). Two histological forms of esophageal cancer exist, namely squamous cell carcinoma (SCC) and Electronic supplementary material The online version of this article (doi:10.1007/s10534-014-9817-5) contains supple- mentary material, which is available to authorized users. Z. Human Á N. M. Sanabria Á M. J. Cronje ´(&) Department of Biochemistry, University of Johannesburg, PO Box 524, Auckland Park, Johannesburg 2006, South Africa e-mail: mariannec@uj.ac.za A. Munyaneza Á B. Omondi Á N. M. Sanabria Á R. Meijboom Department of Chemistry, Research Centre for Synthesis and Catalysis, University of Johannesburg, PO Box 524, Auckland Park, Johannesburg 2006, South Africa e-mail: rmeijboom@uj.ac.za 123 Biometals DOI 10.1007/s10534-014-9817-5