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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

The Antiangiogenic and Antitumoral Activity of Titanocene Y* In Vivo

Author(s): Iduna Fichtner, Diana Behrens, James Claffey, Anthony Deally, Brendan Gleeson, Siddappa Patil, Holger Weber and Matthias Tacke

Volume 8, Issue 4, 2011

Page: [302 - 307] Pages: 6

DOI: 10.2174/157018011794839367

Price: $65


The 4-diethylaminomethylbenzyl-substituted titanocene dichloride (Titanocene Y*), which is completely water- soluble and showed nanomolar activity against the human renal cancer cells CAKI-1, was tested in vitro in an antiangiogenesis assay against human umbilical vein endothelial cells, HUVEC, delivering an IC50 value of 23 +/- 17 μM. Titanocene Y* was then given at 25, 50 and 75 mg/kg/d, on five consecutive days per week for up to three weeks to one cohort of six CAKI-1 tumor-bearing female NMRI:nu/nu mice, while a further cohort was treated with solvent only. At the two higher dosages Titanocene Y* showed high toxicity leading to mortality, while the titanocene-treated mouse cohort treated with the lowest dosage showed a moderate but statistically significant tumor growth reduction with respect to the solvent-treated control group, with an optimal T/C value of 76% at the end of the experiment. Immunohistological analysis revealed that the expression of the proliferation marker Ki-67 was reduced by 21%. Furthermore, anti-angiogenic activity was identified by CD31 staining; the number of micro vessels in a defined tumor area decreased by 23% due to Titanocene Y* treatment. The substance caused dose-dependent body weight loss but did not reduce the number of white blood cells at doses of 25 and 50 mg/kg/d.

Keywords: Anticancer drug, Anti-angiogenic drug, Titanocene, Renal cell cancer, Xenograft, HUVEC, Malignant Disease, Adult Kidney, Adult Malignancies, Adenocarcinoma, Sunitinib, Sorafenib, Temsirolimus, Bevacizumab, dichloride, Tumor area

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