Cytotoxicity of new organometallic Pt(II)-complexes containing 1,10-phenantroline

Among the emerging anti-cancer compounds, phenanthroline derivatives are of high interest. In contrast to cisplatin, phenanthrolines and their metal complexes are potentially intercalant molecules that can interact with DNA by aromatic π-stacking between base pairs. In this study, two new organometallic Pt(II)-complexes containing 1,10-phenantroline (phen), [Pt(phen)(DMSO)(η1CH2CH2OMe)]+, 1, [Pt(phen)(NH3)(η1-CH2CH2OMe)]+, 2, have been taken into consideration in order to evaluate their cytotoxicity in different human cancer cell lines. In addition, maximal intracellular uptake (MIU) was assayed by ICP-AES after incubation of cells with 100 μM 1 and 2 for 0.5-12 hours. Ten different human cancer cell lines (Caco-2, Caki-1, HeLa, Hep-G2, MCF-7, MG-63, SH-SY5Y, Skov-3, ZL-34 and ZL-55) were treated with 1, 2 and cisplatin at increasing concentrations (0.1-200 μM) from 12 to 72 hours to assess their effect on cell viability. While 2 did not show significantly greater cytotoxic effects than cisplatin in any cell line, 1 proved to be highly effective in almost all cell lines and mainly in the first 12-24 hours of treatment (Figure 1). The greater effects were observed in neuroblastoma cells SH-SY5Y (IC50 (12-24 h) between 8.23 ± 1.11 μM and 19.8 ± 3.26 μM) and ovarian adenocarcinoma cells SKOV-3 (IC50 (12-24 h) between 39.8 ± 3.56 μM and 92.13 ± 7.81 μM). ICP-AES in SH-SY5Y and SKOV-3 demonstrated a high intracellular uptake of compound (1) (MIUSH-SY5Y 430.5 ± 40.1 ng Pt/mg protein; MIUSKOV-3 497.6 ± 59.5 ng Pt/mg protein) compared to cisplatin (MIUSH-SY5Y 155.9 ± 31.4 ng Pt/mg protein; MIUSKOV-3 30 ± 10.2 ng Pt/mg protein). Total Pt concentration of compound 2 (MIUSH-SY5Y 300 ± 39.2 ng Pt/mg protein; MIUSKOV-3 140.4 ± 46.3 ng Pt/mg protein) was also higher than cisplatin despite not having significantly greater cytotoxic effects. Further studies are needed in order to evaluate the mechanism of action of both 1 and 2 compounds and therefore understand why compound 1 is more toxic than compound 2. Finally, it is desirable to use healthy cell lines corresponding to the tumor lines used here in order to verify any cellular specificity towards cancer cells of the two compounds.