Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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Antitumor Activity of Oxali-Titanocene Y in Xenografted CAKI-1 Tumors in Mice

Author(s): Iduna Fichtner, Diana Behrens, James Claffey, Brendan Gleeson, Megan Hogan, Denise Wallis, Holger Weber, Matthias Tacke.

Abstract:

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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Article Details

VOLUME: 5
ISSUE: 8
Year: 2008
Page: [489 - 493]
Pages: 5
DOI: 10.2174/157018008786898545
Price: $58