Antitumor activity of vanadocene Y and its selenocyanate derivative in xenografted caki-1 tumors in mice

Abstract: The para-methoxybenzyl-substituted vanadocene dichloride (Vanadocene Y) (1) and its diselenocyanate (Selenocyanato-Vanadocene Y) (2) were tested in vitro in an anti-angiogenesis assay against human umbilical vein endothelial cells (HUVEC) delivering IC50 values of 0.92±0.03μM (1) and 37±11μM (2). In a cytotoxicity assay against the human renal cancer cells, CAKI-1, the compounds demonstrated IC50 values of 0.55±0.09μM (1) and 0.25±0.03μM (2). Then both compounds were given at their maximum tolerable dose, MTD, of 20mg/kg/d (1) or 40mg/kg/d (2) on four consecutive days or at 50% of the MTD on five consecutive days per week for three weeks to overall four cohorts of eight CAKI-1 tumor-bearing female NMRI:nu/nu mice each, while a further cohort was treated with solvent only. Both MTD-treated mouse cohorts showed a statistically significant tumor growth reduction with respect to the solvent-treated control group with an optimal T/C value of 47% on day 39 of the experiment. Immunohistological analysis revealed that the expression of the proliferation marker Ki-67 was reduced due to long-term treatment with 2. [Copyright &y& Elsevier]