The para-methoxybenzyl-substituted titanocene oxalate (Oxali-Titanocene Y) was tested in vitro in an antiangiogenesis assay against human umbilical vein endothelial cells, HUVEC, delivering an IC50 value of 14 μM and in a cytotoxicity assay against the human renal cancer cells, CAKI-1, which demonstrated an IC50 value greater than 100 μM. Then Oxali-Titanocene Y was given at 30 mg/kg/d, which is the maximum tolerable dose, on five consecutive days per week for three weeks to one cohort of eight CAKI-1 tumor-bearing female NMRI:nu/nu mice, while a second cohort was treated with solvent only. The titanocene-treated mouse cohort showed a statistically significant tumor growth reduction with respect to the solvent-treated control group with an optimal T/C value of 38% at the end of the experiment. Immunohistological analysis revealed that the expression of the proliferation marker Ki-67 was reduced by 30%. Furthermore, an anti-angiogenic activity was identified by CD31 staining; the number of micro vessels in a defined tumor area was significantly decreased due to Oxali-Titanocene Y treatment.
Keywords: Anti-cancer drug, Titanocene, Renal-cell cancer, CAKI-1, Cytotoxicity, Xenograft, HUVEC, Anti-angiogenesis
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