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

Item Type:Article
Title:Antitumor activity of vanadocene Y and its selenocyanate derivative in xenografted CAKI-1 tumors in mice
Creators Name:Fichtner, I. and Claffey, J. and Deally, A. and Gleeson, B. and Hogan, M. and Rivera Markelova, M. and Mueller-Bunz, H. and Weber, H. and Tacke, M.
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 ± 0.03 {my}M (1) and 37 ± 11 {my}M (2). In a cytotoxicity assay against the human renal cancer cells, CAKI-1, the compounds demonstrated IC50 values of 0.55 ± 0.09 {my}M (1) and 0.25 ± 0.03 {my}M (2). Then both compounds were given at their maximum tolerable dose, MTD, of 20 mg/kg/d (1) or 40 mg/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.
Keywords:Anticancer Drug, Vanadocene Dichloride, Renal-Cell Cancer, Cytotoxicity, Xenograft, Anti-Angiogenesis
Source:Journal of Organometallic Chemistry
ISSN:0022-328X
Publisher:Elsevier (Switzerland)
Volume:695
Number:8
Page Range:1175-1181
Date:15 April 2010
Official Publication:https://doi.org/10.1016/j.jorganchem.2010.01.026

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