Synergistic antitumor effect of curcumin and dinitrosyl iron complexes for against melanoma cells

The aim of this study was to examine whether combining curcumin, a chemoprevention agent, and dinitrosyl iron complexes (DNICs) would have a synergistic cytotoxic effect on mouse melanoma B16-F10 cells in vitro. Three synthesized DNICs-[PPN] [(NO)(2)Fe(SCH2CONHCH3) 2] (NC01), [PPN] [(NO)(2)Fe(SCH2CON(CH3)(2))(2)] (NC02), and [Na][(NO)(2)Fe(SCH2CON(CH3)(2))(2)] (NC03) were tested in this study. In vitro DNA cleavage assay showed all three DNICs could cause plasmid DNA damage through releasing NO under UV irradiation. The cytotoxicity assay demonstrated these DNICs were toxic to B16-F10 cells in vitro, and the estimated values of LD50 (24 h of incubation) of NC01 and NC02 were 1 mu M, while the values of LD50 of NC03 was 200 mu M. No synergistic cytotoxicity effect was noted in the treatments of the combinations of curcumin and DNICs. On the contrary, in the presence of NC03, the toxicity of curcumin was reduced. Using UV-Visible spectroscopy and fluorescence microscopy, we found NC03 might interact with curcumin and reduce the accumulation of curcumin in cells. Further experiments using the pretreatment of curcumin for 4 h followed by the treatment of NC03 showed the synergistic cytotoxic effect, while, the pretreatment of NC03 followed by the treatment of curcumin did not have any effect. This study provides the basis for further investigation on the effects of combinations of curcumin and other NO donors. (C) 2009 Elsevier B. V. All rights reserved.