Copper, iron, zinc-fluorouracil complexes synthesized in vitro inhibit tumor cell proliferation / 中国组织工程研究

ABSTRACT

BACKGROUND:Anticancer drug and organic metal complexes wil form a new structure or a change in ion concentration, thus changing both the activity and toxicity to produce a synergistic effect. OBJECTIVE:To synthesize new high-efficient and low-toxic metal-fluorouracil complexes as anticancer drugs. METHODS:Copper, zinc and iron salts and fluorouracil were used to synthesize four copper, zinc and iron-fluorouracil complexes that were [Cu(5-Fu)2Cl2], [Cu(5-Fu)2(NO3)2], [Fe(5-Fu)3]SO4 and [Zn(5-Fu)2Cl2]. Preliminary chemical structures of the four complexes were confirmed by elemental analysis and mass spectrometry. Their inhibitory activity on human cancer cells, human leukemia cellline K562 and human colon cancer cellline HCT-116, was measured by MTT colorimetric assay. RESULTS AND CONCLUSION:[Cu(5-Fu)2Cl2], [Cu(5-Fu)2(NO3)2], [Zn(5-Fu)2Cl2] and [Fe(5-Fu)3SO4] were successful y synthesized. These four complexes at a mass concentration of 0.1-100 mg/L inhibited the proliferation of K562 and HCT-116 to different extents. The IC 50 values of these four complexes on K562 and HCT-116 cells were lower than those of fluorouracil, and their cytotoxicity was 1.5-7.8 times higher than that of fluorouracil. To conclude, copper/iron/zinc-fluorouracil complexes exhibit synergic inhibitory effects on cancer cellproliferation.