CYTOTOXIC EFFECTS OF GOLD(III) COMPLEXES ON ESTABLISHED HUMAN TUMOR-CELL LINES SENSITIVE AND RESISTANT TO CISPLATIN

Gold(III) complexes, isostructural and isoelectronic with platinum(II) complexes, are potentially attractive as anticancer agents. We have s ynthesized a group of square planar gold(III) complexes, all containin g at least two gold-chloride bonds in cis-position, and tested their i n vitro cytotoxicity on a panel of established human tumor cell lines. Remarkably, all these compounds showed significant cytotoxic effects. In particular, the complexes containing the salycilaldiminate ligand induced tumor cell growth inhibitory effects comparable to or even gre ater than cisplatin. All gold(III) complexes substantially retained th eir antitumor potency against two cisplatin-resistant tumor cell lines (CCRF-CEM/R leukemia and A2780/R ovarian carcinoma); only minimal cro ss-resistance with cisplatin was observed. When considering the mechan ism of action, it is reasonable to assume that the cytotoxicity of the se gold(III) complexes derives from DNA binding. Preliminary spectrosc opic results are consistent with this hypothesis; indeed, circular dic hroism experiments show that both the salycilaldiminate and the pyridi ne-containing gold(III) complexes bind calf thymus DNA in vitro and al ter reversibly its B-type solution conformation. These results, howeve r, must be treated with caution; solution studies indicate that gold(I II) compounds are poorly stable under physiological conditions, possib ly implying that, when injected, only a small amount will reach, uncha nged, the DNA target. The results of our investigations are discussed in the perspective of future work on the cytotoxic and antitumor prope rties of gold(III) compounds.