Abstract

The indole-substituted titanocene dichloride derivative Titanocene T, which is completely water-soluble and shows micromolar activity against the human renal cancer cells Caki-1, was tested in vivo an against xenografted human renal cell tumors in mice. Titanocene T was then given at 25 and 50 mg/kg, seven times every four days during three weeks to two groups (n=6) of Caki-1 tumor-bearing female NMRI:nu/nu mice, while the control group was treated with solvent only. At both doses Titanocene T induced a moderate to good tumor growth reduction with respect to the solventtreated control group, with an optimal T/C value of 51% and 32% and showed neither mortality nor toxicity. Immunohistochemical analysis revealed that the expression of the proliferation marker Ki-67 was reduced in the high-dosage group. Furthermore, anti-angiogenic activity was identified by CD31 staining; the number of micro vessels in a defined tumor area decreased by 27% and 29% due to Titanocene T treatment.

Keywords: Anticancer drug, anti-angiogenic drug, Titanocene, Renal cell cancer, Xenograft