Tumor inhibition by ferricenium complexes: systemic effect in vivo and cell growth inhibition in vitro

The antiproliferative activity of divers ferricenium complexes [Cp2Fe]+X-(X- = [CC13COO]- X CC13COOH (I); X- = [CC13COOH]- X 2 CC13COOH (II); X- = 1/2 [C13FeOFeC13]2- (III); X- = [FeC14]- (IV); X- = [2,4,6-(NO2)3C6H2O]- (V)) was investigated against solid, subcutaneously growing Ehrlich ascites tumor (EAT) in vivo as well as against EAT cells cultivated in vitro as permanent suspension culture. In vivo, triple intraperitoneal injections of the complexes II (3 X 200 mg/kg), III (3 X 100, 140, 180 mg/kg) or IV (3 X 160 mg/kg) markedly suppressed tumor development thus that the sizes of treated tumors were reduced to 42-48% related to control tumors (100%); these results point to the systemic character of the antitumor action by ferricenium complexes in vivo. In vitro, all ferricenium complexes inhibited cellular proliferation to an equal extent; application of 10(-5) M diminished the increase in cell number by 20-40%, application of 10(-4) M resulted in a total cessation of cellular proliferation. In comparison to cis-diamminedichloroplatinum(II), the cell growth-inhibiting effect of ferricenium complexes was less pronounced and required 10- to 50-fold higher concentration levels to evoke equivalent cytostasis.